Method for using gene expression to determine prognosis of prostate cancer

ABSTRACT

Molecular assays that involve measurement of expression levels of prognostic biomarkers, or co-expressed biomarkers, from a biological sample obtained from a prostate cancer patient, and analysis of the measured expression levels to provide information concerning the likely prognosis for said patient, and likelihood that said patient will have a recurrence of prostate cancer, or to classify the tumor by likelihood of clinical outcome or TMPRSS2 fusion status, are provided herein.

This application claims the benefit of priority to U.S. ProvisionalApplication Nos. 61/368,217, filed Jul. 27, 2010; 61/414,310, filed Nov.16, 2010; and 61/485,536, filed May 12, 2011, all of which are herebyincorporated by reference.

TECHNICAL FIELD

The present disclosure relates to molecular diagnostic assays thatprovide information concerning methods to use gene expression profilesto determine prognostic information for cancer patients. Specifically,the present disclosure provides genes and microRNAs, the expressionlevels of which may be used to determine the likelihood that a prostatecancer patient will experience a local or distant cancer recurrence.

INTRODUCTION

Prostate cancer is the most common solid malignancy in men and thesecond most common cause of cancer-related death in men in North Americaand the European Union (EU). In 2008, over 180,000 patients will bediagnosed with prostate cancer in the United States alone and nearly30,000 will die of this disease. Age is the single most important riskfactor for the development of prostate cancer, and applies across allracial groups that have been studied. With the aging of the U.S.population, it is projected that the annual incidence of prostate cancerwill double by 2025 to nearly 400,000 cases per year.

Since the introduction of prostate-specific antigen (PSA) screening inthe 1990's, the proportion of patients presenting with clinicallyevident disease has fallen dramatically such that patients categorizedas “low risk” now constitute half of new diagnoses today. PSA is used asa tumor marker to determine the presence of prostate cancer as high PSAlevels are associated with prostate cancer. Despite a growing proportionof localized prostate cancer patients presenting with low-risk featuressuch as low stage (T1) disease, greater than 90% of patients in the USstill undergo definitive therapy, including prostatectomy or radiation.Only about 15% of these patients would develop metastatic disease anddie from their prostate cancer, even in the absence of definitivetherapy. A. Bill-Axelson, et al., J Nat'l Cancer Inst. 100(16):1144-1154(2008). Therefore, the majority of prostate cancer patients are beingover-treated.

Estimates of recurrence risk and treatment decisions in prostate cancerare currently based primarily on PSA levels and/or tumor stage. Althoughtumor stage has been demonstrated to have significant association withoutcome sufficient to be included in pathology reports, the College ofAmerican Pathologists Consensus Statement noted that variations inapproach to the acquisition, interpretation, reporting, and analysis ofthis information exist. C. Compton, et al., Arch Pathol Lab Med124:979-992 (2000). As a consequence, existing pathologic stagingmethods have been criticized as lacking reproducibility and thereforemay provide imprecise estimates of individual patient risk.

SUMMARY

This application discloses molecular assays that involve measurement ofexpression level(s) of one or more genes, gene subsets, microRNAs, orone or more microRNAs in combination with one or more genes or genesubsets, from a biological sample obtained from a prostate cancerpatient, and analysis of the measured expression levels to provideinformation concerning the likelihood of cancer recurrence. For example,the likelihood of cancer recurrence could be described in terms of ascore based on clinical or biochemical recurrence-free interval.

In addition, this application discloses molecular assays that involvemeasurement of expression level(s) of one or more genes, gene subsets,microRNAs, or one or more microRNAs in combination with one or moregenes or gene subsets, from a biological sample obtained to identify arisk classification for a prostate cancer patient. For example, patientsmay be stratified using expression level(s) of one or more genes ormicroRNAs associated, positively or negatively, with cancer recurrenceor death from cancer, or with a prognostic factor. In an exemplaryembodiment, the prognostic factor is Gleason pattern.

The biological sample may be obtained from standard methods, includingsurgery, biopsy, or bodily fluids. It may comprise tumor tissue orcancer cells, and, in some cases, histologically normal tissue, e.g.,histologically normal tissue adjacent the tumor tissue. In exemplaryembodiments, the biological sample is positive or negative for a TMPRSS2fusion.

In exemplary embodiments, expression level(s) of one or more genesand/or microRNAs that are associated, positively or negatively, with aparticular clinical outcome in prostate cancer are used to determineprognosis and appropriate therapy. The genes disclosed herein may beused alone or arranged in functional gene subsets, such as celladhesion/migration, immediate-early stress response, and extracellularmatrix-associated. Each gene subset comprises the genes disclosedherein, as well as genes that are co-expressed with one or more of thedisclosed genes. The calculation may be performed on a computer,programmed to execute the gene expression analysis. The microRNAsdisclosed herein may also be used alone or in combination with any oneor more of the microRNAs and/or genes disclosed.

In exemplary embodiments, the molecular assay may involve expressionlevels for at least two genes. The genes, or gene subsets, may beweighted according to strength of association with prognosis or tumormicroenvironment. In another exemplary embodiment, the molecular assaymay involve expression levels of at least one gene and at least onemicroRNA. The gene-microRNA combination may be selected based on thelikelihood that the gene-microRNA combination functionally interact.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 shows the distribution of clinical and pathology assessments ofbiopsy Gleason score, baseline PSA level, and clinical T-stage.

DEFINITIONS

Unless defined otherwise, technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Singleton et al., Dictionary ofMicrobiology and Molecular Biology 2nd ed., J. Wiley & Sons (New York,N.Y. 1994), and March, Advanced Organic Chemistry Reactions, Mechanismsand Structure 4th ed., John Wiley & Sons (New York, N.Y. 1992), provideone skilled in the art with a general guide to many of the terms used inthe present application.

One skilled in the art will recognize many methods and materials similaror equivalent to those described herein, which could be used in thepractice of the present invention. Indeed, the present invention is inno way limited to the methods and materials described herein. Forpurposes of the invention, the following terms are defined below.

The terms “tumor” and “lesion” as used herein, refer to all neoplasticcell growth and proliferation, whether malignant or benign, and allpre-cancerous and cancerous cells and tissues. Those skilled in the artwill realize that a tumor tissue sample may comprise multiple biologicalelements, such as one or more cancer cells, partial or fragmented cells,tumors in various stages, surrounding histologically normal-appearingtissue, and/or macro or micro-dissected tissue.

The terms “cancer” and “cancerous” refer to or describe thephysiological condition in mammals that is typically characterized byunregulated cell growth. Examples of cancer in the present disclosureinclude cancer of the urogenital tract, such as prostate cancer.

The “pathology” of cancer includes all phenomena that compromise thewell-being of the patient. This includes, without limitation, abnormalor uncontrollable cell growth, metastasis, interference with the normalfunctioning of neighboring cells, release of cytokines or othersecretory products at abnormal levels, suppression or aggravation ofinflammatory or immunological response, neoplasia, premalignancy,malignancy, invasion of surrounding or distant tissues or organs, suchas lymph nodes, etc.

As used herein, the term “prostate cancer” is used interchangeably andin the broadest sense refers to all stages and all forms of cancerarising from the tissue of the prostate gland.

According to the tumor, node, metastasis (TNM) staging system of theAmerican Joint Committee on Cancer (AJCC), AJCC Cancer Staging Manual(7th Ed., 2010), the various stages of prostate cancer are defined asfollows: Tumor: T1: clinically inapparent tumor not palpable or visibleby imaging, T1a: tumor incidental histological finding in 5% or less oftissue resected, T1b: tumor incidental histological finding in more than5% of tissue resected, T1c: tumor identified by needle biopsy; T2: tumorconfined within prostate, T2a: tumor involves one half of one lobe orless, T2b: tumor involves more than half of one lobe, but not bothlobes, T2c: tumor involves both lobes; T3: tumor extends through theprostatic capsule, T3a: extracapsular extension (unilateral orbilateral), T3b: tumor invades seminal vesicle(s); T4: tumor is fixed orinvades adjacent structures other than seminal vesicles (bladder neck,external sphincter, rectum, levator muscles, or pelvic wall). Node: NO:no regional lymph node metastasis; N1: metastasis in regional lymphnodes. Metastasis: M0: no distant metastasis; M1: distant metastasispresent.

The Gleason Grading system is used to help evaluate the prognosis of menwith prostate cancer. Together with other parameters, it is incorporatedinto a strategy of prostate cancer staging, which predicts prognosis andhelps guide therapy. A Gleason “score” or “grade” is given to prostatecancer based upon its microscopic appearance. Tumors with a low Gleasonscore typically grow slowly enough that they may not pose a significantthreat to the patients in their lifetimes. These patients are monitored(“watchful waiting” or “active surveillance”) over time. Cancers with ahigher Gleason score are more aggressive and have a worse prognosis, andthese patients are generally treated with surgery (e.g., radicalprostectomy) and, in some cases, therapy (e.g., radiation, hormone,ultrasound, chemotherapy). Gleason scores (or sums) comprise grades ofthe two most common tumor patterns. These patterns are referred to asGleason patterns 1-5, with pattern 1 being the most well-differentiated.Most have a mixture of patterns. To obtain a Gleason score or grade, thedominant pattern is added to the second most prevalent pattern to obtaina number between 2 and 10. The Gleason Grades include: G1: welldifferentiated (slight anaplasia) (Gleason 2-4); G2: moderatelydifferentiated (moderate anaplasia) (Gleason 5-6); G3-4: poorlydifferentiated/undifferentiated (marked anaplasia) (Gleason 7-10).

Stage groupings: Stage I: T1a N0 M0 G1; Stage II: (T1a N0M0G2-4) or(T1b, c, T1, T2, N0 M0 Any G); Stage III: T3 N0 M0 Any G; Stage 1V: (T4N0 M0 Any G) or (Any T N1 M0 Any G) or (Any T Any N M1 Any G).

As used herein, the term “tumor tissue” refers to a biological samplecontaining one or more cancer cells, or a fraction of one or more cancercells. Those skilled in the art will recognize that such biologicalsample may additionally comprise other biological components, such ashistologically appearing normal cells (e.g., adjacent the tumor),depending upon the method used to obtain the tumor tissue, such assurgical resection, biopsy, or bodily fluids.

As used herein, the term “AUA risk group” refers to the 2007 updatedAmerican Urological Association (AUA) guidelines for management ofclinically localized prostate cancer, which clinicians use to determinewhether a patient is at low, intermediate, or high risk of biochemical(PSA) relapse after local therapy.

As used herein, the term “adjacent tissue (AT)” refers to histologically“normal” cells that are adjacent a tumor. For example, the AT expressionprofile may be associated with disease recurrence and survival.

As used herein “non-tumor prostate tissue” refers to histologicallynormal-appearing tissue adjacent a prostate tumor.

Prognostic factors are those variables related to the natural history ofcancer, which influence the recurrence rates and outcome of patientsonce they have developed cancer. Clinical parameters that have beenassociated with a worse prognosis include, for example, increased tumorstage, PSA level at presentation, and Gleason grade or pattern.Prognostic factors are frequently used to categorize patients intosubgroups with different baseline relapse risks.

The term “prognosis” is used herein to refer to the likelihood that acancer patient will have a cancer-attributable death or progression,including recurrence, metastatic spread, and drug resistance, of aneoplastic disease, such as prostate cancer. For example, a “goodprognosis” would include long term survival without recurrence and a“bad prognosis” would include cancer recurrence.

As used herein, the term “expression level” as applied to a gene refersto the normalized level of a gene product, e.g. the normalized valuedetermined for the RNA expression level of a gene or for the polypeptideexpression level of a gene.

The term “gene product” or “expression product” are used herein to referto the RNA (ribonucleic acid) transcription products (transcripts) ofthe gene, including mRNA, and the polypeptide translation products ofsuch RNA transcripts. A gene product can be, for example, an unsplicedRNA, an mRNA, a splice variant mRNA, a microRNA, a fragmented RNA, apolypeptide, a post-translationally modified polypeptide, a splicevariant polypeptide, etc.

The term “RNA transcript” as used herein refers to the RNA transcriptionproducts of a gene, including, for example, mRNA, an unspliced RNA, asplice variant mRNA, a microRNA, and a fragmented RNA.

The term “microRNA” is used herein to refer to a small, non-coding,single-stranded RNA of ˜18-25 nucleotides that may regulate geneexpression. For example, when associated with the RNA-induced silencingcomplex (RISC), the complex binds to specific mRNA targets and causestranslation repression or cleavage of these mRNA sequences.

Unless indicated otherwise, each gene name used herein corresponds tothe Official Symbol assigned to the gene and provided by Entrez Gene(URL: www.ncbi.nlm.nih.gov/sites/entrez) as of the filing date of thisapplication.

The terms “correlated” and “associated” are used interchangeably hereinto refer to the association between two measurements (or measuredentities). The disclosure provides genes, gene subsets, microRNAs, ormicroRNAs in combination with genes or gene subsets, the expressionlevels of which are associated with tumor stage. For example, theincreased expression level of a gene or microRNA may be positivelycorrelated (positively associated) with a good or positive prognosis.Such a positive correlation may be demonstrated statistically in variousways, e.g. by a cancer recurrence hazard ratio less than one. In anotherexample, the increased expression level of a gene or microRNA may benegatively correlated (negatively associated) with a good or positiveprognosis. In that case, for example, the patient may experience acancer recurrence.

The terms “good prognosis” or “positive prognosis” as used herein referto a beneficial clinical outcome, such as long-term survival withoutrecurrence. The terms “bad prognosis” or “negative prognosis” as usedherein refer to a negative clinical outcome, such as cancer recurrence.

The term “risk classification” means a grouping of subjects by the levelof risk (or likelihood) that the subject will experience a particularclinical outcome. A subject may be classified into a risk group orclassified at a level of risk based on the methods of the presentdisclosure, e.g. high, medium, or low risk. A “risk group” is a group ofsubjects or individuals with a similar level of risk for a particularclinical outcome.

The term “long-term” survival is used herein to refer to survival for aparticular time period, e.g., for at least 5 years, or for at least 10years.

The term “recurrence” is used herein to refer to local or distantrecurrence (i.e., metastasis) of cancer. For example, prostate cancercan recur locally in the tissue next to the prostate or in the seminalvesicles. The cancer may also affect the surrounding lymph nodes in thepelvis or lymph nodes outside this area. Prostate cancer can also spreadto tissues next to the prostate, such as pelvic muscles, bones, or otherorgans. Recurrence can be determined by clinical recurrence detected by,for example, imaging study or biopsy, or biochemical recurrence detectedby, for example, sustained follow-up prostate-specific antigen (PSA)levels ≧0.4 ng/mL or the initiation of salvage therapy as a result of arising PSA level.

The term “clinical recurrence-free interval (cRFI)” is used herein astime (in months) from surgery to first clinical recurrence or death dueto clinical recurrence of prostate cancer. Losses due to incompletefollow-up, other primary cancers or death prior to clinical recurrenceare considered censoring events; when these occur, the only informationknown is that up through the censoring time, clinical recurrence has notoccurred in this subject. Biochemical recurrences are ignored for thepurposes of calculating cRFI.

The term “biochemical recurrence-free interval (bRFI)” is used herein tomean the time (in months) from surgery to first biochemical recurrenceof prostate cancer. Clinical recurrences, losses due to incompletefollow-up, other primary cancers, or death prior to biochemicalrecurrence are considered censoring events.

The term “Overall Survival (OS)” is used herein to refer to the time (inmonths) from surgery to death from any cause. Losses due to incompletefollow-up are considered censoring events. Biochemical recurrence andclinical recurrence are ignored for the purposes of calculating OS.

The term “Prostate Cancer-Specific Survival (PCSS)” is used herein todescribe the time (in years) from surgery to death from prostate cancer.Losses due to incomplete follow-up or deaths from other causes areconsidered censoring events. Clinical recurrence and biochemicalrecurrence are ignored for the purposes of calculating PCSS.

The term “upgrading” or “upstaging” as used herein refers to a change inGleason grade from 3+3 at the time of biopsy to 3+4 or greater at thetime of radical prostatectomy (RP), or Gleason grade 3+4 at the time ofbiopsy to 4+3 or greater at the time of RP, or seminal vessicalinvolvement (SVI), or extracapsular involvement (ECE) at the time of RP.

In practice, the calculation of the measures listed above may vary fromstudy to study depending on the definition of events to be consideredcensored.

The term “microarray” refers to an ordered arrangement of hybridizablearray elements, e.g. oligonucleotide or polynucleotide probes, on asubstrate.

The term “polynucleotide” generally refers to any polyribonucleotide orpolydeoxribonucleotide, which may be unmodified RNA or DNA or modifiedRNA or DNA. Thus, for instance, polynucleotides as defined hereininclude, without limitation, single- and double-stranded DNA, DNAincluding single- and double-stranded regions, single- anddouble-stranded RNA, and RNA including single- and double-strandedregions, hybrid molecules comprising DNA and RNA that may besingle-stranded or, more typically, double-stranded or include single-and double-stranded regions. In addition, the term “polynucleotide” asused herein refers to triple-stranded regions comprising RNA or DNA orboth RNA and DNA. The strands in such regions may be from the samemolecule or from different molecules. The regions may include all of oneor more of the molecules, but more typically involve only a region ofsome of the molecules. One of the molecules of a triple-helical regionoften is an oligonucleotide. The term “polynucleotide” specificallyincludes cDNAs. The term includes DNAs (including cDNAs) and RNAs thatcontain one or more modified bases. Thus, DNAs or RNAs with backbonesmodified for stability or for other reasons, are “polynucleotides” asthat term is intended herein. Moreover, DNAs or RNAs comprising unusualbases, such as inosine, or modified bases, such as tritiated bases, areincluded within the term “polynucleotides” as defined herein. Ingeneral, the term “polynucleotide” embraces all chemically,enzymatically and/or metabolically modified forms of unmodifiedpolynucleotides, as well as the chemical forms of DNA and RNAcharacteristic of viruses and cells, including simple and complex cells.

The term “oligonucleotide” refers to a relatively short polynucleotide,including, without limitation, single-stranded deoxyribonucleotides,single- or double-stranded ribonucleotides, RNArDNA hybrids anddouble-stranded DNAs. Oligonucleotides, such as single-stranded DNAprobe oligonucleotides, are often synthesized by chemical methods, forexample using automated oligonucleotide synthesizers that arecommercially available. However, oligonucleotides can be made by avariety of other methods, including in vitro recombinant DNA-mediatedtechniques and by expression of DNAs in cells and organisms.

The term “Ct” as used herein refers to threshold cycle, the cycle numberin quantitative polymerase chain reaction (qPCR) at which thefluorescence generated within a reaction well exceeds the definedthreshold, i.e. the point during the reaction at which a sufficientnumber of amplicons have accumulated to meet the defined threshold.

The term “Cp” as used herein refers to “crossing point.” The Cp value iscalculated by determining the second derivatives of entire qPCRamplification curves and their maximum value. The Cp value representsthe cycle at which the increase of fluorescence is highest and where thelogarithmic phase of a PCR begins.

The terms “threshold” or “thresholding” refer to a procedure used toaccount for non-linear relationships between gene expressionmeasurements and clinical response as well as to further reducevariation in reported patient scores. When thresholding is applied, allmeasurements below or above a threshold are set to that threshold value.Non-linear relationship between gene expression and outcome could beexamined using smoothers or cubic splines to model gene expression inCox PH regression on recurrence free interval or logistic regression onrecurrence status. D. Cox, Journal of the Royal Statistical Society,Series B 34:187-220 (1972). Variation in reported patient scores couldbe examined as a function of variability in gene expression at the limitof quantitation and/or detection for a particular gene.

As used herein, the term “amplicon,” refers to pieces of DNA that havebeen synthesized using amplification techniques, such as polymerasechain reactions (PCR) and ligase chain reactions.

“Stringency” of hybridization reactions is readily determinable by oneof ordinary skill in the art, and generally is an empirical calculationdependent upon probe length, washing temperature, and saltconcentration. In general, longer probes require higher temperatures forproper annealing, while shorter probes need lower temperatures.Hybridization generally depends on the ability of denatured DNA tore-anneal when complementary strands are present in an environment belowtheir melting temperature. The higher the degree of desired homologybetween the probe and hybridizable sequence, the higher the relativetemperature which can be used. As a result, it follows that higherrelative temperatures would tend to make the reaction conditions morestringent, while lower temperatures less so. For additional details andexplanation of stringency of hybridization reactions, see Ausubel etal., Current Protocols in Molecular Biology (Wiley IntersciencePublishers, 1995).

“Stringent conditions” or “high stringency conditions”, as definedherein, typically: (1) employ low ionic strength and high temperaturefor washing, for example 0.015 M sodium chloride/0.0015 M sodiumcitrate/0.1% sodium dodecyl sulfate at 50° C.; (2) employ duringhybridization a denaturing agent, such as formamide, for example, 50%(v/v) formamide with 0.1% bovine serum albumin/0.1% Ficoll/0.1%polyvinylpyrrolidone/50 mM sodium phosphate buffer at pH 6.5 with 750 mMsodium chloride, 75 mM sodium citrate at 42° C.; or (3) employ 50%formamide, 5×SSC (0.75 M NaCl, 0.075 M sodium citrate), 50 mM sodiumphosphate (pH 6.8), 0.1% sodium pyrophosphate, 5×Denhardt's solution,sonicated salmon sperm DNA (50 μg/ml), 0.1% SDS, and 10% dextran sulfateat 42° C., with washes at 42° C. in 0.2×SSC (sodium chloride/sodiumcitrate) and 50% formamide, followed by a high-stringency washconsisting of 0.1×SSC containing EDTA at 55° C.

“Moderately stringent conditions” may be identified as described bySambrook et al., Molecular Cloning: A Laboratory Manual, New York: ColdSpring Harbor Press, 1989, and include the use of washing solution andhybridization conditions (e.g., temperature, ionic strength and % SDS)less stringent that those described above. An example of moderatelystringent conditions is overnight incubation at 37° C. in a solutioncomprising: 20% formamide, 5×SSC (150 mM NaCl, 15 mM trisodium citrate),50 mM sodium phosphate (pH 7.6), 5×Denhardt's solution, 10% dextransulfate, and 20 mg/ml denatured sheared salmon sperm DNA, followed bywashing the filters in 1×SSC at about 37-500 C. The skilled artisan willrecognize how to adjust the temperature, ionic strength, etc. asnecessary to accommodate factors such as probe length and the like.

The terms “splicing” and “RNA splicing” are used interchangeably andrefer to RNA processing that removes introns and joins exons to producemature mRNA with continuous coding sequence that moves into thecytoplasm of an eukaryotic cell.

The terms “co-express” and “co-expressed”, as used herein, refer to astatistical correlation between the amounts of different transcriptsequences across a population of different patients. Pairwiseco-expression may be calculated by various methods known in the art,e.g., by calculating Pearson correlation coefficients or Spearmancorrelation coefficients. Co-expressed gene cliques may also beidentified using graph theory. An analysis of co-expression may becalculated using normalized expression data. A gene is said to beco-expressed with a particular disclosed gene when the expression levelof the gene exhibits a Pearson correlation coefficient greater than orequal to 0.6.

A “computer-based system” refers to a system of hardware, software, anddata storage medium used to analyze information. The minimum hardware ofa patient computer-based system comprises a central processing unit(CPU), and hardware for data input, data output (e.g., display), anddata storage. An ordinarily skilled artisan can readily appreciate thatany currently available computer-based systems and/or components thereofare suitable for use in connection with the methods of the presentdisclosure. The data storage medium may comprise any manufacturecomprising a recording of the present information as described above, ora memory access device that can access such a manufacture.

To “record” data, programming or other information on a computerreadable medium refers to a process for storing information, using anysuch methods as known in the art. Any convenient data storage structuremay be chosen, based on the means used to access the stored information.A variety of data processor programs and formats can be used forstorage, e.g. word processing text file, database format, etc.

A “processor” or “computing means” references any hardware and/orsoftware combination that will perform the functions required of it. Forexample, a suitable processor may be a programmable digitalmicroprocessor such as available in the form of an electroniccontroller, mainframe, server or personal computer (desktop orportable). Where the processor is programmable, suitable programming canbe communicated from a remote location to the processor, or previouslysaved in a computer program product (such as a portable or fixedcomputer readable storage medium, whether magnetic, optical or solidstate device based). For example, a magnetic medium or optical disk maycarry the programming, and can be read by a suitable readercommunicating with each processor at its corresponding station.

As used herein, the terms “active surveillance” and “watchful waiting”mean closely monitoring a patient's condition without giving anytreatment until symptoms appear or change. For example, in prostatecancer, watchful waiting is usually used in older men with other medicalproblems and early-stage disease.

As used herein, the term “surgery” applies to surgical methodsundertaken for removal of cancerous tissue, including pelviclymphadenectomy, radical prostatectomy, transurethral resection of theprostate (TURP), excision, dissection, and tumor biopsy/removal. Thetumor tissue or sections used for gene expression analysis may have beenobtained from any of these methods.

As used herein, the term “therapy” includes radiation, hormonal therapy,cryosurgery, chemotherapy, biologic therapy, and high-intensity focusedultrasound.

As used herein, the term “TMPRSS fusion” and “TMPRSS2 fusion” are usedinterchangeably and refer to a fusion of the androgen-driven TMPRSS2gene with the ERG oncogene, which has been demonstrated to have asignificant association with prostate cancer. S. Perner, et al., UrologeA. 46(7):754-760 (2007); S. A. Narod, et al., Br J Cancer 99(6):847-851(2008). As used herein, positive TMPRSS fusion status indicates that theTMPRSS fusion is present in a tissue sample, whereas negative TMPRSSfusion status indicates that the TMPRSS fusion is not present in atissue sample. Experts skilled in the art will recognize that there arenumerous ways to determine TMPRSS fusion status, such as real-time,quantitative PCR or high-throughput sequencing. See, e.g., K. Mertz, etal., Neoplasis 9(3):200-206 (2007); C. Maher, Nature 458(7234):97-101(2009).

Gene Expression Methods Using Genes, Gene Subsets, and microRNAs

The present disclosure provides molecular assays that involvemeasurement of expression level(s) of one or more genes, gene subsets,microRNAs, or one or more microRNAs in combination with one or moregenes or gene subsets, from a biological sample obtained from a prostatecancer patient, and analysis of the measured expression levels toprovide information concerning the likelihood of cancer recurrence.

The present disclosure further provides methods to classify a prostatetumor based on expression level(s) of one or more genes and/ormicroRNAs. The disclosure further provides genes and/or microRNAs thatare associated, positively or negatively, with a particular prognosticoutcome. In exemplary embodiments, the clinical outcomes include cRFIand bRFI. In another embodiment, patients may be classified in riskgroups based on the expression level(s) of one or more genes and/ormicroRNAs that are associated, positively or negatively, with aprognostic factor. In an exemplary embodiment, that prognostic factor isGleason pattern.

Various technological approaches for determination of expression levelsof the disclosed genes and microRNAs are set forth in thisspecification, including, without limitation, RT-PCR, microarrays,high-throughput sequencing, serial analysis of gene expression (SAGE)and Digital Gene Expression (DGE), which will be discussed in detailbelow. In particular aspects, the expression level of each gene ormicroRNA may be determined in relation to various features of theexpression products of the gene including exons, introns, proteinepitopes and protein activity.

The expression level(s) of one or more genes and/or microRNAs may bemeasured in tumor tissue. For example, the tumor tissue may obtainedupon surgical removal or resection of the tumor, or by tumor biopsy. Thetumor tissue may be or include histologically “normal” tissue, forexample histologically “normal” tissue adjacent to a tumor. Theexpression level of genes and/or microRNAs may also be measured in tumorcells recovered from sites distant from the tumor, for examplecirculating tumor cells, body fluid (e.g., urine, blood, blood fraction,etc.).

The expression product that is assayed can be, for example, RNA or apolypeptide. The expression product may be fragmented. For example, theassay may use primers that are complementary to target sequences of anexpression product and could thus measure full transcripts as well asthose fragmented expression products containing the target sequence.Further information is provided in Table A (inserted in specificationprior to claims).

The RNA expression product may be assayed directly or by detection of acDNA product resulting from a PCR-based amplification method, e.g.,quantitative reverse transcription polymerase chain reaction (qRT-PCR).(See e.g., U.S. Pat. No. 7,587,279). Polypeptide expression product maybe assayed using immunohistochemistry (IHC). Further, both RNA andpolypeptide expression products may also be is assayed usingmicroarrays.

Clinical Utility

Prostate cancer is currently diagnosed using a digital rectal exam (DRE)and Prostate-specific antigen (PSA) test. If PSA results are high,patients will generally undergo a prostate tissue biopsy. Thepathologist will review the biopsy samples to check for cancer cells anddetermine a Gleason score. Based on the Gleason score, PSA, clinicalstage, and other factors, the physician must make a decision whether tomonitor the patient, or treat the patient with surgery and therapy.

At present, clinical decision-making in early stage prostate cancer isgoverned by certain histopathologic and clinical factors. These include:(1) tumor factors, such as clinical stage (e.g. T1, T2), PSA level atpresentation, and Gleason grade, that are very strong prognostic factorsin determining outcome; and (2) host factors, such as age at diagnosisand co-morbidity. Because of these factors, the most clinically usefulmeans of stratifying patients with localized disease according toprognosis has been through multifactorial staging, using the clinicalstage, the serum PSA level, and tumor grade (Gleason grade) together. Inthe 2007 updated American Urological Association (AUA) guidelines formanagement of clinically localized prostate cancer, these parametershave been grouped to determine whether a patient is at low,intermediate, or high risk of biochemical (PSA) relapse after localtherapy. I. Thompson, et al., Guideline for the management of clinicallylocalized prostate cancer, J Urol. 177(6):2106-31 (2007).

Although such classifications have proven to be helpful indistinguishing patients with localized disease who may need adjuvanttherapy after surgery/radiation, they have less ability to discriminatebetween indolent cancers, which do not need to be treated with localtherapy, and aggressive tumors, which require local therapy. In fact,these algorithms are of increasingly limited use for deciding betweenconservative management and definitive therapy because the bulk ofprostate cancers diagnosed in the PSA screening era now present withclinical stage T1c and PSA ≦10 ng/mL.

Patients with T1 prostate cancer have disease that is not clinicallyapparent but is discovered either at transurethral resection of theprostate (TURP, T1a, T1b) or at biopsy performed because of an elevatedPSA (>4 ng/mL, T1c). Approximately 80% of the cases presenting in 2007are clinical T1 at diagnosis. In a Scandinavian trial, OS at 10 yearswas 85% for patients with early stage prostate cancer (T1/T2) andGleason score ≦7, after radical prostatectomy.

Patients with T2 prostate cancer have disease that is clinically evidentand is organ confined; patients with T3 tumors have disease that haspenetrated the prostatic capsule and/or has invaded the seminalvesicles. It is known from surgical series that clinical stagingunderestimates pathological stage, so that about 20% of patients who areclinically T2 will be pT3 after prostatectomy. Most of patients with T2or T3 prostate cancer are treated with local therapy, eitherprostatectomy or radiation. The data from the Scandinavian trial suggestthat for T2 patients with Gleason grade ≦7, the effect of prostatectomyon survival is at most 5% at 10 years; the majority of patients do notbenefit from surgical treatment at the time of diagnosis. For T2patients with Gleason >7 or for T3 patients, the treatment effect ofprostatectomy is assumed to be significant but has not been determinedin randomized trials. It is known that these patients have a significantrisk (10-30%) of recurrence at 10 years after local treatment, however,there are no prospective randomized trials that define the optimal localtreatment (radical prostatectomy, radiation) at diagnosis, whichpatients are likely to benefit from neo-adjuvant/adjuvant androgendeprivation therapy, and whether treatment (androgen deprivation,chemotherapy) at the time of biochemical failure (elevated PSA) has anyclinical benefit.

Accurately determining Gleason scores from needle biopsies presentsseveral technical challenges. First, interpreting histology that is“borderline” between Gleason pattern is highly subjective, even forurologic pathologists. Second, incomplete biopsy sampling is yet anotherreason why the “predicted” Gleason score on biopsy does not alwayscorrelate with the actual “observed” Gleason score of the prostatecancer in the gland itself. Hence, the accuracy of Gleason scoring isdependent upon not only the expertise of the pathologist reading theslides, but also on the completeness and adequacy of the prostate biopsysampling strategy. T. Stamey, Urology 45:2-12 (1995). The gene/microRNAexpression assay and associated information provided by the practice ofthe methods disclosed herein provide a molecular assay method tofacilitate optimal treatment decision-making in early stage prostatecancer. An exemplary embodiment provides genes and microRNAs, theexpression levels of which are associated (positively or negatively)with prostate cancer recurrence. For example, such a clinical tool wouldenable physicians to identify T2/T3 patients who are likely to recurfollowing definitive therapy and need adjuvant treatment.

In addition, the methods disclosed herein may allow physicians toclassify tumors, at a molecular level, based on expression level(s) ofone or more genes and/or microRNAs that are significantly associatedwith prognostic factors, such as Gleason pattern and TMPRSS fusionstatus. These methods would not be impacted by the technicaldifficulties of intra-patient variability, histologically determiningGleason pattern in biopsy samples, or inclusion of histologically normalappearing tissue adjacent to tumor tissue. Multi-analyte gene/microRNAexpression tests can be used to measure the expression level of one ormore genes and/or microRNAs involved in each of several relevantphysiologic processes or component cellular characteristics. The methodsdisclosed herein may group the genes and/or microRNAs. The grouping ofgenes and microRNAs may be performed at least in part based on knowledgeof the contribution of those genes and/or microRNAs according tophysiologic functions or component cellular characteristics, such as inthe groups discussed above. Furthermore, one or more microRNAs may becombined with one or moregenes. The gene-microRNA combination may beselected based on the likelihood that the gene-microRNA combinationfunctionally interact. The formation of groups (or gene subsets), inaddition, can facilitate the mathematical weighting of the contributionof various expression levels to cancer recurrence. The weighting of agene/microRNA group representing a physiological process or componentcellular characteristic can reflect the contribution of that process orcharacteristic to the pathology of the cancer and clinical outcome.

Optionally, the methods disclosed may be used to classify patients byrisk, for example risk of recurrence. Patients can be partitioned intosubgroups (e.g., tertiles or quartiles) and the values chosen willdefine subgroups of patients with respectively greater or lesser risk.

The utility of a disclosed gene marker in predicting prognosis may notbe unique to that marker. An alternative marker having an expressionpattern that is parallel to that of a disclosed gene may be substitutedfor, or used in addition to, that co-expressed gene or microRNA. Due tothe co-expression of such genes or microRNAs, substitution of expressionlevel values should have little impact on the overall utility of thetest. The closely similar expression patterns of two genes or microRNAsmay result from involvement of both genes or microRNAs in the sameprocess and/or being under common regulatory control in prostate tumorcells. The present disclosure thus contemplates the use of suchco-expressed genes, gene subsets, or microRNAs as substitutes for, or inaddition to, genes of the present disclosure.

Methods of Assaying Expression Levels of a Gene Product

The methods and compositions of the present disclosure will employ,unless otherwise indicated, conventional techniques of molecular biology(including recombinant techniques), microbiology, cell biology, andbiochemistry, which are within the skill of the art. Exemplarytechniques are explained fully in the literature, such as, “MolecularCloning: A Laboratory Manual”, 2nd edition (Sambrook et al., 1989);“Oligonucleotide Synthesis” (M. J. Gait, ed., 1984); “Animal CellCulture” (R. I. Freshney, ed., 1987); “Methods in Enzymology” (AcademicPress, Inc.); “Handbook of Experimental Immunology”, 4th edition (D. M.Weir & C. C. Blackwell, eds., Blackwell Science Inc., 1987); “GeneTransfer Vectors for Mammalian Cells” (J. M. Miller & M. P. Calos, eds.,1987); “Current Protocols in Molecular Biology” (F. M. Ausubel et al.,eds., 1987); and “PCR: The Polymerase Chain Reaction”, (Mullis et al.,eds., 1994).

Methods of gene expression profiling include methods based onhybridization analysis of polynucleotides, methods based on sequencingof polynucleotides, and proteomics-based methods. Exemplary methodsknown in the art for the quantification of RNA expression in a sampleinclude northern blotting and in situ hybridization (Parker & Barnes,Methods in Molecular Biology 106:247-283 (1999)); RNAse protectionassays (Hod, Biotechniques 13:852-854 (1992)); and PCR-based methods,such as reverse transcription PCT (RT-PCR) (Weis et al., Trends inGenetics 8:263-264 (1992)). Antibodies may be employed that canrecognize sequence-specific duplexes, including DNA duplexes, RNAduplexes, and DNA-RNA hybrid duplexes or DNA-protein duplexes.Representative methods for sequencing-based gene expression analysisinclude Serial Analysis of Gene Expression (SAGE), and gene expressionanalysis by massively parallel signature sequencing (MPSS).

Reverse Transcriptase PCR (RT-PCR)

Typically, mRNA or microRNA is isolated from a test sample. The startingmaterial is typically total RNA isolated from a human tumor, usuallyfrom a primary tumor. Optionally, normal tissues from the same patientcan be used as an internal control. Such normal tissue can behistologically-appearing normal tissue adjacent a tumor. mRNA ormicroRNA can be extracted from a tissue sample, e.g., from a sample thatis fresh, frozen (e.g. fresh frozen), or paraffin-embedded and fixed(e.g. formalin-fixed).

General methods for mRNA and microRNA extraction are well known in theart and are disclosed in standard textbooks of molecular biology,including Ausubel et al., Current Protocols of Molecular Biology, JohnWiley and Sons (1997). Methods for RNA extraction from paraffin embeddedtissues are disclosed, for example, in Rupp and Locker, Lab Invest.56:A67 (1987), and De Andrés et al., BioTechniques 18:42044 (1995). Inparticular, RNA isolation can be performed using a purification kit,buffer set and protease from commercial manufacturers, such as Qiagen,according to the manufacturer's instructions. For example, total RNAfrom cells in culture can be isolated using Qiagen RNeasy mini-columns.Other commercially available RNA isolation kits include MasterPure™Complete DNA and RNA Purification Kit (EPICENTRE®, Madison, Wis.), andParaffin Block RNA Isolation Kit (Ambion, Inc.). Total RNA from tissuesamples can be isolated using RNA Stat-60 (Tel-Test). RNA prepared fromtumor can be isolated, for example, by cesium chloride density gradientcentrifugation.

The sample containing the RNA is then subjected to reverse transcriptionto produce cDNA from the RNA template, followed by exponentialamplification in a PCR reaction. The two most commonly used reversetranscriptases are avilo myeloblastosis virus reverse transcriptase(AMV-RT) and Moloney murine leukemia virus reverse transcriptase(MMLV-RT). The reverse transcription step is typically primed usingspecific primers, random hexamers, or oligo-dT primers, depending on thecircumstances and the goal of expression profiling. For example,extracted RNA can be reverse-transcribed using a GeneAmp RNA PCR kit(Perkin Elmer, Calif., USA), following the manufacturer's instructions.The derived cDNA can then be used as a template in the subsequent PCRreaction.

PCR-based methods use a thermostable DNA-dependent DNA polymerase, suchas a Taq DNA polymerase. For example, TaqMan® PCR typically utilizes the5′-nuclease activity of Taq or Tth polymerase to hydrolyze ahybridization probe bound to its target amplicon, but any enzyme withequivalent 5′ nuclease activity can be used. Two oligonucleotide primersare used to generate an amplicon typical of a PCR reaction product. Athird oligonucleotide, or probe, can be designed to facilitate detectionof a nucleotide sequence of the amplicon located between thehybridization sites the two PCR primers. The probe can be detectablylabeled, e.g., with a reporter dye, and can further be provided withboth a fluorescent dye, and a quencher fluorescent dye, as in a Taqman®probe configuration. Where a Taqman® probe is used, during theamplification reaction, the Taq DNA polymerase enzyme cleaves the probein a template-dependent manner. The resultant probe fragmentsdisassociate in solution, and signal from the released reporter dye isfree from the quenching effect of the second fluorophore. One moleculeof reporter dye is liberated for each new molecule synthesized, anddetection of the unquenched reporter dye provides the basis forquantitative interpretation of the data.

TaqMan® RT-PCR can be performed using commercially available equipment,such as, for example, high-throughput platforms such as the ABI PRISM7700 Sequence Detection System® (Perkin-Elmer-Applied Biosystems, FosterCity, Calif., USA), or Lightcycler (Roche Molecular Biochemicals,Mannheim, Germany). In a preferred embodiment, the procedure is run on aLightCycler® 480 (Roche Diagnostics) real-time PCR system, which is amicrowell plate-based cycler platform.

5′-Nuclease assay data are commonly initially expressed as a thresholdcycle (“C_(T)”). Fluorescence values are recorded during every cycle andrepresent the amount of product amplified to that point in theamplification reaction. The threshold cycle (C_(T)) is generallydescribed as the point when the fluorescent signal is first recorded asstatistically significant. Alternatively, data may be expressed as acrossing point (“Cp”). The Cp value is calculated by determining thesecond derivatives of entire qPCR amplification curves and their maximumvalue. The Cp value represents the cycle at which the increase offluorescence is highest and where the logarithmic phase of a PCR begins.

To minimize errors and the effect of sample-to-sample variation, RT-PCRis usually performed using an internal standard. The ideal internalstandard gene (also referred to as a reference gene) is expressed at aquite constant level among cancerous and non-cancerous tissue of thesame origin (i.e., a level that is not significantly different amongnormal and cancerous tissues), and is not significantly affected by theexperimental treatment (i.e., does not exhibit a significant differencein expression level in the relevant tissue as a result of exposure tochemotherapy), and expressed at a quite constant level among the sametissue taken from different patients. For example, reference genesuseful in the methods disclosed herein should not exhibit significantlydifferent expression levels in cancerous prostate as compared to normalprostate tissue. RNAs frequently used to normalize patterns of geneexpression are mRNAs for the housekeeping genesglyceraldehyde-3-phosphate-dehydrogenase (GAPDH) and (3-actin. Exemplaryreference genes used for normalization comprise one or more of thefollowing genes: AAMP, ARF1, ATP5E, CLTC, GPS1, and PGK1. Geneexpression measurements can be normalized relative to the mean of one ormore (e.g., 2, 3, 4, 5, or more) reference genes. Reference-normalizedexpression measurements can range from 2 to 15, where a one unitincrease generally reflects a 2-fold increase in RNA quantity.

Real time PCR is compatible both with quantitative competitive PCR,where internal competitor for each target sequence is used fornormalization, and with quantitative comparative PCR using anormalization gene contained within the sample, or a housekeeping genefor RT-PCR. For further details see, e.g. Held et al., Genome Research6:986-994 (1996).

The steps of a representative protocol for use in the methods of thepresent disclosure use fixed, paraffin-embedded tissues as the RNAsource. For example, mRNA isolation, purification, primer extension andamplification can be performed according to methods available in theart. (see, e.g., Godfrey et al. J. Molec. Diagnostics 2: 84-91 (2000);Specht et al., Am. J. Pathol. 158: 419-29 (2001)). Briefly, arepresentative process starts with cutting about 10 μm thick sections ofparaffin-embedded tumor tissue samples. The RNA is then extracted, andprotein and DNA depleted from the RNA-containing sample. After analysisof the RNA concentration, RNA is reverse transcribed using gene specificprimers followed by RT-PCR to provide for cDNA amplification products.

Design of Intron-Based PCR Primers and Probes

PCR primers and probes can be designed based upon exon or intronsequences present in the mRNA transcript of the gene of interest.Primer/probe design can be performed using publicly available software,such as the DNA BLAT software developed by Kent, W. J., Genome Res.12(4):656-64 (2002), or by the BLAST software including its variations.

Where necessary or desired, repetitive sequences of the target sequencecan be masked to mitigate non-specific signals. Exemplary tools toaccomplish this include the Repeat Masker program available on-linethrough the Baylor College of Medicine, which screens DNA sequencesagainst a library of repetitive elements and returns a query sequence inwhich the repetitive elements are masked. The masked intron sequencescan then be used to design primer and probe sequences using anycommercially or otherwise publicly available primer/probe designpackages, such as Primer Express (Applied Biosystems); MGBassay-by-design (Applied Biosystems); Primer3 (Steve Rozen and Helen J.Skaletsky (2000) Primer3 on the WWW for general users and for biologistprogrammers. See S. Rrawetz, S. Misener, Bioinformatics Methods andProtocols: Methods in Molecular Biology, pp. 365-386 (Humana Press).

Other factors that can influence PCR primer design include primerlength, melting temperature (Tm), and G/C content, specificity,complementary primer sequences, and 3′-end sequence. In general, optimalPCR primers are generally 17-30 bases in length, and contain about20-80%, such as, for example, about 50-60% G+C bases, and exhibit Tm'sbetween 50 and 80° C., e.g. about 50 to 70° C.

For further guidelines for PCR primer and probe design see, e.g.Dieffenbach, CW. et al, “General Concepts for PCR Primer Design” in: PCRPrimer, A Laboratory Manual, Cold Spring Harbor Laboratory Press,. NewYork, 1995, pp. 133-155; Innis and Gelfand, “Optimization of PCRs” in:PCR Protocols, A Guide to Methods and Applications, CRC Press, London,1994, pp. 5-11; and Plasterer, T. N. Primerselect: Primer and probedesign. Methods Mol. Biol. 70:520-527 (1997), the entire disclosures ofwhich are hereby expressly incorporated by reference.

Table A provides further information concerning the primer, probe, andamplicon sequences associated with the Examples disclosed herein.

MassARRAY® System

In MassARRAY-based methods, such as the exemplary method developed bySequenom, Inc. (San Diego, Calif.) following the isolation of RNA andreverse transcription, the obtained cDNA is spiked with a synthetic DNAmolecule (competitor), which matches the targeted cDNA region in allpositions, except a single base, and serves as an internal standard. ThecDNA/competitor mixture is PCR amplified and is subjected to a post-PCRshrimp alkaline phosphatase (SAP) enzyme treatment, which results in thedephosphorylation of the remaining nucleotides. After inactivarion ofthe alkaline phosphatase, the PCR products from the competitor and cDNAare subjected to primer extension, which generates distinct mass signalsfor the competitor- and cDNA-derives PCR products. After purification,these products are dispensed on a chip array, which is pre-loaded withcomponents needed for analysis with matrix-assisted laser desorptionionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis. ThecDNA present in the reaction is then quantified by analyzing the ratiosof the peak areas in the mass spectrum generated. For further detailssee, e.g. Ding and Cantor, Proc. Natl. Acad. Sci. USA 100:3059-3064(2003).

Other PCR-Based Methods

Further PCR-based techniques that can find use in the methods disclosedherein include, for example, BeadArray® technology (Illumina, San Diego,Calif.; Oliphant et al., Discovery of Markers for Disease (Supplement toBiotechniques), June 2002; Ferguson et al., Analytical Chemistry 72:5618(2000)); BeadsArray for Detection of Gene Expression® (BADGE), using thecommercially available LuminexlOO LabMAP® system and multiplecolor-coded microspheres (Luminex Corp., Austin, Tex.) in a rapid assayfor gene expression (Yang et al., Genome Res. 11:1888-1898 (2001)); andhigh coverage expression profiling (HiCEP) analysis (Fukumura et al.,Nucl. Acids. Res. 31(16) e94 (2003).

Microarrays

Expression levels of a gene or microArray of interest can also beassessed using the microarray technique. In this method, polynucleotidesequences of interest (including cDNAs and oligonucleotides) are arrayedon a substrate. The arrayed sequences are then contacted underconditions suitable for specific hybridization with detectably labeledcDNA generated from RNA of a test sample. As in the RT-PCR method, thesource of RNA typically is total RNA isolated from a tumor sample, andoptionally from normal tissue of the same patient as an internal controlor cell lines. RNA can be extracted, for example, from frozen orarchived paraffin-embedded and fixed (e.g. formalin-fixed) tissuesamples.

For example, PCR amplified inserts of cDNA clones of a gene to beassayed are applied to a substrate in a dense array. Usually at least10,000 nucleotide sequences are applied to the substrate. For example,the microarrayed genes, immobilized on the microchip at 10,000 elementseach, are suitable for hybridization under stringent conditions.Fluorescently labeled cDNA probes may be generated through incorporationof fluorescent nucleotides by reverse transcription of RNA extractedfrom tissues of interest. Labeled cDNA probes applied to the chiphybridize with specificity to each spot of DNA on the array. Afterwashing under stringent conditions to remove non-specifically boundprobes, the chip is scanned by confocal laser microscopy or by anotherdetection method, such as a CCD camera. Quantitation of hybridization ofeach arrayed element allows for assessment of corresponding RNAabundance.

With dual color fluorescence, separately labeled cDNA probes generatedfrom two sources of RNA are hybridized pair wise to the array. Therelative abundance of the transcripts from the two sources correspondingto each specified gene is thus determined simultaneously. Theminiaturized scale of the hybridization affords a convenient and rapidevaluation of the expression pattern for large numbers of genes. Suchmethods have been shown to have the sensitivity required to detect raretranscripts, which are expressed at a few copies per cell, and toreproducibly detect at least approximately two-fold differences in theexpression levels (Schena et at, Proc. Natl. Acad. ScL USA 93(2):106-149(1996)). Microarray analysis can be performed by commercially availableequipment, following manufacturer's protocols, such as by using theAffymetrix GenChip® technology, or Incyte's microarray technology.

Serial Analysis of Gene Expression (SAGE)

Serial analysis of gene expression (SAGE) is a method that allows thesimultaneous and quantitative analysis of a large number of genetranscripts, without the need of providing an individual hybridizationprobe for each transcript. First, a short sequence tag (about 10-14 bp)is generated that contains sufficient information to uniquely identify atranscript, provided that the tag is obtained from a unique positionwithin each transcript. Then, many transcripts are linked together toform long serial molecules, that can be sequenced, revealing theidentity of the multiple tags simultaneously. The expression pattern ofany population of transcripts can be quantitatively evaluated bydetermining the abundance of individual tags, and identifying the genecorresponding to each tag. For more details see, e.g. Velculescu et al.,Science 270:484-487 (1995); and Velculescu et al., Cell 88:243-51(1997).

Gene Expression Analysis by Nucleic Acid Sequencing

Nucleic acid sequencing technologies are suitable methods for analysisof gene expression. The principle underlying these methods is that thenumber of times a cDNA sequence is detected in a sample is directlyrelated to the relative expression of the RNA corresponding to thatsequence. These methods are sometimes referred to by the term DigitalGene Expression (DGE) to reflect the discrete numeric property of theresulting data. Early methods applying this principle were SerialAnalysis of Gene Expression (SAGE) and Massively Parallel SignatureSequencing (MPSS). See, e.g., S. Brenner, et al., Nature Biotechnology18(6):630-634 (2000). More recently, the advent of “next-generation”sequencing technologies has made DGE simpler, higher throughput, andmore affordable. As a result, more laboratories are able to utilize DGEto screen the expression of more genes in more individual patientsamples than previously possible. See, e.g., J. Marioni, Genome Research18(9):1509-1517 (2008); R. Morin, Genome Research 18(4):610-621 (2008);A. Mortazavi, Nature Methods 5(7):621-628 (2008); N. Cloonan, NatureMethods 5(7):613-619 (2008).

Isolating RNA from Body Fluids

Methods of isolating RNA for expression analysis from blood, plasma andserum (see, e.g., K. Enders, et al., Clin Chem 48, 1647-53 (2002) (andreferences cited therein) and from urine (see, e.g., R. Boom, et al., JClin Microbiol. 28, 495-503 (1990) and references cited therein) havebeen described.

Immunohistochemistry

Immunohistochemistry methods are also suitable for detecting theexpression levels of genes and applied to the method disclosed herein.Antibodies (e.g., monoclonal antibodies) that specifically bind a geneproduct of a gene of interest can be used in such methods. Theantibodies can be detected by direct labeling of the antibodiesthemselves, for example, with radioactive labels, fluorescent labels,hapten’ labels such as, biotin, or an enzyme such as horse radishperoxidase or alkaline phosphatase. Alternatively, unlabeled primaryantibody can be used in conjunction with a labeled secondary antibodyspecific for the primary antibody. Immunohistochemistry protocols andkits are well known in the art and are commercially available.

Proteomics

The term “proteome” is defined as the totality of the proteins presentin a sample (e.g. tissue, organism, or cell culture) at a certain pointof time. Proteomics includes, among other things, study of the globalchanges of protein expression in a sample (also referred to as“expression proteomics”). Proteomics typically includes the followingsteps: (1) separation of individual proteins in a sample by 2-D gelelectrophoresis (2-D PAGE); (2) identification of the individualproteins recovered from the gel, e.g. my mass spectrometry or N-terminalsequencing, and (3) analysis of the data using bioinformatics.

General Description of the mRNA/microRNA Isolation, Purification andAmplification

The steps of a representative protocol for profiling gene expressionusing fixed, paraffin-embedded tissues as the RNA source, including mRNAor microRNA isolation, purification, primer extension and amplificationare provided in various published journal articles. (See, e.g., T. E.Godfrey, et al., J. Molec. Diagnostics 2: 84-91 (2000); K. Specht etal., Am. J. Pathol. 158: 419-29 (2001), M. Cronin, et al., Am J Pathol164:35-42 (2004)). Briefly, a representative process starts with cuttinga tissue sample section (e.g. about 10 μm thick sections of aparaffin-embedded tumor tissue sample). The RNA is then extracted, andprotein and DNA are removed. After analysis of the RNA concentration,RNA repair is performed if desired. The sample can then be subjected toanalysis, e.g., by reverse transcribed using gene specific promotersfollowed by RT-PCR.

Statistical Analysis of Expression Levels in Identification of Genes andmicroRNAs

One skilled in the art will recognize that there are many statisticalmethods that may be used to determine whether there is a significantrelationship between a parameter of interest (e.g., recurrence) andexpression levels of a marker gene/microRNA as described here. In anexemplary embodiment, the present invention provides a stratified cohortsampling design (a form of case-control sampling) using tissue and datafrom prostate cancer patients. Selection of specimens was stratified byT stage (T1, T2), year cohort (<1993, ≧1993), and prostatectomy GleasonScore (low/intermediate, high). All patients with clinical recurrencewere selected and a sample of patients who did not experience a clinicalrecurrence was selected. For each patient, up to two enriched tumorspecimens and one normal-appearing tissue sample was assayed.

All hypothesis tests were reported using two-sided p-values. Toinvestigate if there is a significant relationship of outcomes (clinicalrecurrence-free interval (cRFI), biochemical recurrence-free interval(bRFI), prostate cancer-specific survival (PCSS), and overall survival(OS)) with individual genes and/or microRNAs, demographic or clinicalcovariates Cox Proportional Hazards (PH) models using maximum weightedpseudo partial-likelihood estimators were used and p-values from Waldtests of the null hypothesis that the hazard ratio (HR) is one arereported. To investigate if there is a significant relationship betweenindividual genes and/or microRNAs and Gleason pattern of a particularsample, ordinal logistic regression models using maximum weightedlikelihood methods were used and p-values from Wald tests of the nullhypothesis that the odds ratio (OR) is one are reported.

Coexpression Analysis

The present disclosure provides a method to determine tumor stage basedon the expression of staging genes, or genes that co-express withparticular staging genes. To perform particular biological processes,genes often work together in a concerted way, i.e. they areco-expressed. Co-expressed gene groups identified for a disease processlike cancer can serve as biomarkers for tumor status and diseaseprogression. Such co-expressed genes can be assayed in lieu of, or inaddition to, assaying of the staging gene with which they areco-expressed.

In an exemplary embodiment, the joint correlation of gene expressionlevels among prostate cancer specimens under study may be assessed. Forthis purpose, the correlation structures among genes and specimens maybe examined through hierarchical cluster methods. This information maybe used to confirm that genes that are known to be highly correlated inprostate cancer specimens cluster together as expected. Only genesexhibiting a nominally significant (unadjusted p<0.05) relationship withcRFI in the univariate Cox PH regression analysis will be included inthese analyses.

One skilled in the art will recognize that many co-expression analysismethods now known or later developed will fall within the scope andspirit of the present invention. These methods may incorporate, forexample, correlation coefficients, co-expression network analysis,clique analysis, etc., and may be based on expression data from RT-PCR,microarrays, sequencing, and other similar technologies. For example,gene expression clusters can be identified using pair-wise analysis ofcorrelation based on Pearson or Spearman correlation coefficients. (See,e.g., Pearson K. and Lee A., Biometrika 2, 357 (1902); C. Spearman,Amer. J. Psychol 15:72-101 (1904); J. Myers, A. Well, Research Designand Statistical Analysis, p. 508 (2nd Ed., 2003).)

Normalization of Expression Levels

The expression data used in the methods disclosed herein can benormalized. Normalization refers to a process to correct for (normalizeaway), for example, differences in the amount of RNA assayed andvariability in the quality of the RNA used, to remove unwanted sourcesof systematic variation in Ct or Cp measurements, and the like. Withrespect to RT-PCR experiments involving archived fixed paraffin embeddedtissue samples, sources of systematic variation are known to include thedegree of RNA degradation relative to the age of the patient sample andthe type of fixative used to store the sample. Other sources ofsystematic variation are attributable to laboratory processingconditions.

Assays can provide for normalization by incorporating the expression ofcertain normalizing genes, which do not significantly differ inexpression levels under the relevant conditions. Exemplary normalizationgenes disclosed herein include housekeeping genes. (See, e.g., E.Eisenberg, et al., Trends in Genetics 19(7):362-365 (2003).)Normalization can be based on the mean or median signal (Ct or Cp) ofall of the assayed genes or a large subset thereof (global normalizationapproach). In general, the normalizing genes, also referred to asreference genes should be genes that are known not to exhibitsignificantly different expression in prostate cancer as compared tonon-cancerous prostate tissue, and are not significantly affected byvarious sample and process conditions, thus provide for normalizing awayextraneous effects.

In exemplary embodiments, one or more of the following genes are used asreferences by which the mRNA or microRNA expression data is normalized:AAMP, ARF1, ATP5E, CLTC, GPS1, and PGK1. In another exemplaryembodiment, one or more of the following microRNAs are used asreferences by which the expression data of microRNAs are normalized:hsa-miR-106a; hsa-miR-146b-5p; hsa-miR-191; hsa-miR-19b; andhsa-miR-92a. The calibrated weighted average C_(T) or Cp measurementsfor each of the prognostic and predictive genes or microRNAs may benormalized relative to the mean of five or more reference genes ormicroRNAs.

Those skilled in the art will recognize that normalization may beachieved in numerous ways, and the techniques described above areintended only to be exemplary, not exhaustive.

Standardization of Expression Levels

The expression data used in the methods disclosed herein can bestandardized. Standardization refers to a process to effectively put allthe genes or microRNAs on a comparable scale. This is performed becausesome genes or microRNAs will exhibit more variation (a broader range ofexpression) than others. Standardization is performed by dividing eachexpression value by its standard deviation across all samples for thatgene or microRNA. Hazard ratios are then interpreted as the relativerisk of recurrence per 1 standard deviation increase in expression.

Kits of the Invention

The materials for use in the methods of the present invention are suitedfor preparation of kits produced in accordance with well-knownprocedures. The present disclosure thus provides kits comprising agents,which may include gene (or microRNA)-specific or gene (ormicroRNA)-selective probes and/or primers, for quantifying theexpression of the disclosed genes or microRNAs for predicting prognosticoutcome or response to treatment. Such kits may optionally containreagents for the extraction of RNA from tumor samples, in particularfixed paraffin-embedded tissue samples and/or reagents for RNAamplification. In addition, the kits may optionally comprise thereagent(s) with an identifying description or label or instructionsrelating to their use in the methods of the present invention. The kitsmay comprise containers (including microliter plates suitable for use inan automated implementation of the method), each with one or more of thevarious materials or reagents (typically in concentrated form) utilizedin the methods, including, for example, chromatographic columns,pre-fabricated microarrays, buffers, the appropriate nucleotidetriphosphates (e.g., dATP, dCTP, dGTP and dTTP; or rATP, rCTP, rGTP andUTP), reverse transcriptase, DNA polymerase, RNA polymerase, and one ormore probes and primers of the present invention (e.g., appropriatelength poly(T) or random primers linked to a promoter reactive with theRNA polymerase). Mathematical algorithms used to estimate or quantifyprognostic or predictive information are also properly potentialcomponents of kits.

Reports

The methods of this invention, when practiced for commercial diagnosticpurposes, generally produce a report or summary of information obtainedfrom the herein-described methods. For example, a report may includeinformation concerning expression levels of one or more genes and/ormicroRNAs, classification of the tumor or the patient's risk ofrecurrence, the patient's likely prognosis or risk classification,clinical and pathologic factors, and/or other information. The methodsand reports of this invention can further include storing the report ina database. The method can create a record in a database for the subjectand populate the record with data. The report may be a paper report, anauditory report, or an electronic record. The report may be displayedand/or stored on a computing device (e.g., handheld device, desktopcomputer, smart device, website, etc.). It is contemplated that thereport is provided to a physician and/or the patient. The receiving ofthe report can further include establishing a network connection to aserver computer that includes the data and report and requesting thedata and report from the server computer.

Computer Program

The values from the assays described above, such as expression data, canbe calculated and stored manually. Alternatively, the above-describedsteps can be completely or partially performed by a computer programproduct. The present invention thus provides a computer program productincluding a computer readable storage medium having a computer programstored on it. The program can, when read by a computer, execute relevantcalculations based on values obtained from analysis of one or morebiological sample from an individual (e.g., gene expression levels,normalization, standardization, thresholding, and conversion of valuesfrom assays to a score and/or text or graphical depiction of tumor stageand related information). The computer program product has storedtherein a computer program for performing the calculation.

The present disclosure provides systems for executing the programdescribed above, which system generally includes: a) a central computingenvironment; b) an input device, operatively connected to the computingenvironment, to receive patient data, wherein the patient data caninclude, for example, expression level or other value obtained from anassay using a biological sample from the patient, or microarray data, asdescribed in detail above; c) an output device, connected to thecomputing environment, to provide information to a user (e.g., medicalpersonnel); and d) an algorithm executed by the central computingenvironment (e.g., a processor), where the algorithm is executed basedon the data received by the input device, and wherein the algorithmcalculates an expression score, thresholding, or other functionsdescribed herein. The methods provided by the present invention may alsobe automated in whole or in part.

All aspects of the present invention may also be practiced such that alimited number of additional genes and/or microRNAs that areco-expressed or functionally related with the disclosed genes, forexample as evidenced by statistically meaningful Pearson and/or Spearmancorrelation coefficients, are included in a test in addition to and/orin place of disclosed genes.

Having described the invention, the same will be more readily understoodthrough reference to the following Examples, which are provided by wayof illustration, and are not intended to limit the invention in any way.

EXAMPLES Example 1 RNA Yield and Gene Expression Profiles in ProstateCancer Biopsy Cores

Clinical tools based on prostate needle core biopsies are needed toguide treatment planning at diagnosis for men with localized prostatecancer. Limiting tissue in needle core biopsy specimens posessignificant challenges to the development of molecular diagnostic tests.This study examined RNA extraction yields and gene expression profilesusing an RT-PCR assay to characterize RNA from manually micro-dissectedfixed paraffin embedded (FPE) prostate cancer needle biopsy cores. Italso investigated the association of RNA yields and gene expressionprofiles with Gleason score in these specimens.

Patients and Samples

This study determined the feasibility of gene expression profileanalysis in prostate cancer needle core biopsies by evaluating thequantity and quality of RNA extracted from fixed paraffin-embedded (FPE)prostate cancer needle core biopsy specimens. Forty-eight (48)formalin-fixed blocks from prostate needle core biopsy specimens wereused for this study. Classification of specimens was based oninterpretation of the Gleason score (2005 Int'l Society of UrologicalPathology Consensus Conference) and percentage tumor (<33%,33-66%, >66%) involvement as assessed by pathologists.

TABLE 1 Distribution of cases Gleason score ~<33% ~33-66% ~>66% CategoryTumor Tumor Tumor Low (≦6) 5 5 6 Intermediate (7) 5 5 6 High (8, 9, 10)5 5 6 Total 15 15 18

Assay Methods

Fourteen (14) serial 5 μm unstained sections from each FPE tissue blockwere included in the study. The first and last sections for each casewere H&E stained and histologically reviewed to confirm the presence oftumor and for tumor enrichment by manual micro-dissection.

RNA from enriched tumor samples was extracted using a manual RNAextraction process. RNA was quantitated using the RiboGreen® assay andtested for the presence of genomic DNA contamination. Samples withsufficient RNA yield and free of genomic DNA tested for gene expressionlevels of a 24-gene panel of reference and cancer-related genes usingquantitative RT-PCR. The expression was normalized to the average of 6reference genes (AAMP, ARF1, ATP5E, CLTC, EEF1A1, and GPX1).

Statistical Methods

Descriptive statistics and graphical displays were used to summarizestandard pathology metrics and gene expression, with stratification forGleason Score category and percentage tumor involvement category.Ordinal logistic regression was used to evaluate the relationshipbetween gene expression and Gleason Score category.

Results

The RNA yield per unit surface area ranged from 16 to 2406 ng/mm2.Higher RNA yield was observed in samples with higher percent tumorinvolvement (p=0.02) and higher Gleason score (p=0.01). RNA yield wassufficient (>200 ng) in 71% of cases to permit 96-well RT-PCR, with 87%of cases having >100 ng RNA yield. The study confirmed that geneexpression from prostate biopsies, as measured by qRT-PCR, wascomparable to FPET samples used in commercial molecular assays forbreast cancer. In addition, it was observed that greater biopsy RNAyields are found with higher Gleason score and higher percent tumorinvolvement. Nine genes were identified as significantly associated withGleason score (p<0.05) and there was a large dynamic range observed formany test genes.

Example 2 Gene Expression Analysis for Genes Associated with Prognosisin Prostate Cancer

Patients and Samples

Approximately 2600 patients with clinical stage T1/T2 prostate cancertreated with radical prostatectomy (RP) at the Cleveland Clinic between1987 and 2004 were identified. Patients were excluded from the studydesign if they received neo-adjuvant and/or adjuvant therapy, ifpre-surgical PSA levels were missing, or if no tumor block was availablefrom initial diagnosis. 127 patients with clinical recurrence and 374patients without clinical recurrence after radical prostatectomy wererandomly selected using a cohort sampling design. The specimens werestratified by T stage (T1, T2), year cohort (<1993, ≧1993), andprostatectomy Gleason score (low/intermediate, high). Of the 501 sampledpatients, 51 were excluded for insufficient tumor; 7 were excluded dueto clinical ineligibility; 2 were excluded due to poor quality of geneexpression data; and 10 were excluded because primary Gleason patternwas unavailable. Thus, this gene expression study included tissue anddata from 111 patients with clinical recurrence and 330 patients withoutclinical recurrence after radical prostatectomies performed between 1987and 2004 for treatment of early stage (T1, T2) prostate cancer.

Two fixed paraffin embedded (FPE) tissue specimens were obtained fromprostate tumor specimens in each patient. The sampling method (samplingmethod A or B) depended on whether the highest Gleason pattern is alsothe primary Gleason pattern. For each specimen selected, the invasivecancer cells were at least 5.0 mm in dimension, except in the instancesof pattern 5, where 2.2 mm was accepted. Specimens were spatiallydistinct where possible.

TABLE 2 Sampling Methods Sampling Method A Sampling Method B Forpatients whose prostatectomy For patients whose prostatectomy primaryGleason pattern is also primary Gleason pattern is not the highestGleason pattern the highest Gleason pattern Specimen 1 (A1) = primarySpecimen 1 (B1) = highest Gleason pattern Gleason pattern Select andmark largest focus Select highest Gleason pattern tissue (greatestcross-sectional area) of from spatially distinct area from primaryGleason pattern tissue. specimen B2, if possible. Invasive Invasivecancer area ≧5.0 mm. cancer area at least 5.0 mm if selecting secondarypattern, at least 2.2 mm if selecting Gleason pattern 5. Specimen 2 (A2)= secondary Specimen 2 (B2) = primary Gleason pattern Gleason patternSelect and mark secondary Gleason Select largest focus (greatest patterntissue from spatially cross-sectional area) of primary distinct areafrom specimen A1. Gleason pattern tissue. Invasive Invasive cancer area≧5.0 mm. cancer area ≧5.0 mm.

Histologically normal appearing tissue (NAT) adjacent to the tumorspecimen (also referred to in these Examples as “non-tumor tissue”) wasalso evaluated. Adjacent tissue was collected 3 mm from the tumor to 3mm from the edge of the FPET block. NAT was preferentially sampledadjacent to the primary Gleason pattern. In cases where there wasinsufficient NAT adjacent to the primary Gleason pattern, then NAT wassampled adjacent to the secondary or highest Gleason pattern (A2 or B1)per the method set forth in Table 2. Six (6) 10 μm sections withbeginning H&E at 5 μm and ending unstained slide at 5 μm were preparedfrom each fixed paraffin-embedded tumor (FPET) block included in thestudy. All cases were histologically reviewed and manuallymicro-dissected to yield two enriched tumor samples and, where possible,one normal tissue sample adjacent to the tumor specimen.

Assay Method

In this study, RT-PCR analysis was used to determine RNA expressionlevels for 738 genes and chromosomal rearrangements (e.g., TMPRSS2-ERGfusion or other ETS family genes) in prostate cancer tissue andsurrounding NAT in patients with early-stage prostate cancer treatedwith radical prostatectomy.

The samples were quantified using the RiboGreen assay and a subsettested for presence of genomic DNA contamination. Samples were takeninto reverse transcription (RT) and quantitative polymerase chainreaction (qPCR). All analyses were conducted on reference-normalizedgene expression levels using the average of the of replicate wellcrossing point (CP) values for the 6 reference genes (AAMP, ARF1, ATP5E,CLTC, GPS1, PGK1).

Statistical Analysis and Results

Primary statistical analyses involved 111 patients with clinicalrecurrence and 330 patients without clinical recurrence after radicalprostatectomy for early-stage prostate cancer stratified by T-stage (T1,T2), year cohort (<1993, ≧1993), and prostatectomy Gleason score(low/intermediate, high). Gleason score categories are defined asfollows: low (Gleason score ≦6), intermediate (Gleason score=7), andhigh (Gleason score ≧8). A patient was included in a specified analysisif at least one sample for that patient was evaluable. Unless otherwisestated, all hypothesis tests were reported using two-sided p-values. Themethod of Storey was applied to the resulting set of p-values to controlthe false discovery rate (FDR) at 20%. J. Storey, R. Tibshirani,Estimating the Positive False Discovery Rate Under Dependence, withApplications to DNA Microarrays, Dept. of Statistics, Stanford Univ.(2001).

Analysis of gene expression and recurrence-free interval was based onunivariate Cox Proportional Hazards (PH) models using maximum weightedpseudo-partial-likelihood estimators for each evaluable gene in the genelist (727 test genes and 5 reference genes). P-values were generatedusing Wald tests of the null hypothesis that the hazard ratio (HR) isone. Both unadjusted p-values and the q-value (smallest FDR at which thehypothesis test in question is rejected) were reported. Un-adjustedp-values <0.05 were considered statistically significant. Since twotumor specimens were selected for each patient, this analysis wasperformed using the 2 specimens from each patient as follows: (1)analysis using the primary Gleason pattern specimen from each patient(Specimens A1 and B2 as described in Table 2); (2) analysis using thehighest Gleason pattern specimen from each patient (Specimens A1 and B1as described in Table 2).

Analysis of gene expression and Gleason pattern (3, 4, 5) was based onunivariate ordinal logistic regression models using weighted maximumlikelihood estimators for each gene in the gene list (727 test genes and5 reference genes). P-values were generated using a Wald test of thenull hypothesis that the odds ratio (OR) is one. Both unadjustedp-values and the q-value (smallest FDR at which the hypothesis test inquestion is rejected) were reported. Un-adjusted p-values <0.05 wereconsidered statistically significant. Since two tumor specimens wereselected for each patient, this analysis was performed using the 2specimens from each patient as follows: (1) analysis using the primaryGleason pattern specimen from each patient (Specimens A1 and B2 asdescribed in Table 2); (2) analysis using the highest Gleason patternspecimen from each patient (Specimens A1 and B1 as described in Table2).

It was determined whether there is a significant relationship betweencRFI and selected demographic, clinical, and pathology variables,including age, race, clinical tumor stage, pathologic tumor stage,location of selected tumor specimens within the prostate (peripheralversus transitional zone), PSA at the time of surgery, overall Gleasonscore from the radical prostatectomy, year of surgery, and specimenGleason pattern. Separately for each demographic or clinical variable,the relationship between the clinical covariate and cRFI was modeledusing univariate Cox PH regression using weighted pseudopartial-likelihood estimators and a p-value was generated using Wald'stest of the null hypothesis that the hazard ratio (HR) is one.Covariates with unadjusted p-values <0.2 may have been included in thecovariate-adjusted analyses.

It was determined whether there was a significant relationship betweeneach of the individual cancer-related genes and cRFI after controllingfor important demographic and clinical covariates. Separately for eachgene, the relationship between gene expression and cRFI was modeledusing multivariate Cox PH regression using weighted pseudopartial-likelihood estimators including important demographic andclinical variables as covariates. The independent contribution of geneexpression to the prediction of cRFI was tested by generating a p-valuefrom a Wald test using a model that included clinical covariates foreach nodule (specimens as defined in Table 2). Un-adjusted p-values<0.05 were considered statistically significant.

Tables 3A and 3B provide genes significantly associated (p<0.05),positively or negatively, with Gleason pattern in the primary and/orhighest Gleason pattern. Increased expression of genes in Table 3A ispositively associated with higher Gleason score, while increasedexpression of genes in Table 3B are negatively associated with higherGleason score.

TABLE 3A Table 3A Gene significantly (p < 0.05) associated with Gleasonpattern for all specimens in the primary Gleason pattern or highestGleason pattern odds ratio (OR) > 1.0 (Increased expression ispositively associated with higher Gleason Score) Primary Pattern HighestPattern Official Symbol OR p-value OR p-value ALCAM 1.73 <.001 1.360.009 ANLN 1.35 0.027 APOC1 1.47 0.005 1.61 <.001 APOE 1.87 <.001 2.15<.001 ASAP2 1.53 0.005 ASPN 2.62 <.001 2.13 <.001 ATP5E 1.35 0.035 AURKA1.44 0.010 AURKB 1.59 <.001 1.56 <.001 BAX 1.43 0.006 BGN 2.58 <.0012.82 <.001 BIRC5 1.45 0.003 1.79 <.001 BMP6 2.37 <.001 1.68 <.001 BMPR1B1.58 0.002 BRCA2 1.45 0.013 BUB1 1.73 <.001 1.57 <.001 CACNA1D 1.310.045 1.31 0.033 CADPS 1.30 0.023 CCNB1 1.43 0.023 CCNE2 1.52 0.003 1.320.035 CD276 2.20 <.001 1.83 <.001 CD68 1.36 0.022 CDC20 1.69 <.001 1.95<.001 CDC6 1.38 0.024 1.46 <.001 CDH11 1.30 0.029 CDKN2B 1.55 0.001 1.330.023 CDKN2C 1.62 <.001 1.52 <.001 CDKN3 1.39 0.010 1.50 0.002 CENPF1.96 <.001 1.71 <.001 CHRAC1 1.34 0.022 CLDN3 1.37 0.029 COL1A1 2.23<.001 2.22 <.001 COL1A2 1.42 0.005 COL3A1 1.90 <.001 2.13 <.001 COL8A11.88 <.001 2.35 <.001 CRISP3 1.33 0.040 1.26 0.050 CTHRC1 2.01 <.0011.61 <.001 CTNND2 1.48 0.007 1.37 0.011 DAPK1 1.44 0.014 DIAPH1 1.340.032 1.79 <.001 DIO2 1.56 0.001 DLL4 1.38 0.026 1.53 <.001 ECE1 1.540.012 1.40 0.012 ENY2 1.35 0.046 1.35 0.012 EZH2 1.39 0.040 F2R 2.37<.001 2.60 <.001 FAM49B 1.57 0.002 1.33 0.025 FAP 2.36 <.001 1.89 <.001FCGR3A 2.10 <.001 1.83 <.001 GNPTAB 1.78 <.001 1.54 <.001 GSK3B 1.390.018 HRAS 1.62 0.003 HSD17B4 2.91 <.001 1.57 <.001 HSPA8 1.48 0.0121.34 0.023 IFI30 1.64 <.001 1.45 0.013 IGFBP3 1.29 0.037 IL11 1.52 0.0011.31 0.036 INHBA 2.55 <.001 2.30 <.001 ITGA4 1.35 0.028 JAG1 1.68 <.0011.40 0.005 KCNN2 1.50 0.004 KCTD12 1.38 0.012 KHDRBS3 1.85 <.001 1.72<.001 KIF4A 1.50 0.010 1.50 <.001 KLK14 1.49 0.001 1.35 <.001 KPNA2 1.680.004 1.65 0.001 KRT2 1.33 0.022 KRT75 1.27 0.028 LAMC1 1.44 0.029LAPTM5 1.36 0.025 1.31 0.042 LTBP2 1.42 0.023 1.66 <.001 MANF 1.34 0.019MAOA 1.55 0.003 1.50 <.001 MAP3K5 1.55 0.006 1.44 0.001 MDK 1.47 0.0131.29 0.041 MDM2 1.31 0.026 MELK 1.64 <.001 1.64 <.001 MMP11 2.33 <.0011.66 <.001 MYBL2 1.41 0.007 1.54 <.001 MYO6 1.32 0.017 NETO2 1.36 0.018NOX4 1.84 <.001 1.73 <.001 NPM1 1.68 0.001 NRIP3 1.36 0.009 NRP1 1.800.001 1.36 0.019 OSM 1.33 0.046 PATE1 1.38 0.032 PECAM1 1.38 0.021 1.310.035 PGD 1.56 0.010 PLK1 1.51 0.004 1.49 0.002 PLOD2 1.29 0.027 POSTN1.70 0.047 1.55 0.006 PPP3CA 1.38 0.037 1.37 0.006 PTK6 1.45 0.007 1.53<.001 PTTG1 1.51 <.001 RAB31 1.31 0.030 RAD21 2.05 <.001 1.38 0.020RAD51 1.46 0.002 1.26 0.035 RAF1 1.46 0.017 RALBP1 1.37 0.043 RHOC 1.330.021 ROBO2 1.52 0.003 1.41 0.006 RRM2 1.77 <.001 1.50 <.001 SAT1 1.670.002 1.61 <.001 SDC1 1.66 0.001 1.46 0.014 SEC14L1 1.53 0.003 1.62<.001 SESN3 1.76 <.001 1.45 <.001 SFRP4 2.69 <.001 2.03 <.001 SHMT2 1.690.007 1.45 0.003 SKIL 1.46 0.005 SOX4 1.42 0.016 1.27 0.031 SPARC 1.400.024 1.55 <.001 SPINK1 1.29 0.002 SPP1 1.51 0.002 1.80 <.001 TFDP1 1.480.014 THBS2 1.87 <.001 1.65 <.001 THY1 1.58 0.003 1.64 <.001 TK1 1.79<.001 1.42 0.001 TOP2A 2.30 <.001 2.01 <.001 TPD52 1.95 <.001 1.30 0.037TPX2 2.12 <.001 1.86 <.001 TYMP 1.36 0.020 TYMS 1.39 0.012 1.31 0.036UBE2C 1.66 <.001 1.65 <.001 UBE2T 1.59 <.001 1.33 0.017 UGDH 1.28 0.049UGT2B15 1.46 0.001 1.25 0.045 UHRF1 1.95 <.001 1.62 <.001 VDR 1.43 0.0101.39 0.018 WNT5A 1.54 0.001 1.44 0.013

TABLE 3B Table 3B. Gene significantly (p < 0.05) associated with Gleasonpattern for all specimens in the primary Gleason pattern or highestGleason pattern odds ratio (OR) < 1.0 (Increased expression isnegatively associated with higher Gleason score) Primary Highest PatternPattern Official Symbol OR p-value OR p-value ABCA5 0.78 0.041 ABCG20.65 0.001 0.72 0.012 ACOX2 0.44 <.001 0.53 <.001 ADH5 0.45 <.001 0.42<.001 AFAP1 0.79 0.038 AIG1 0.77 0.024 AKAP1 0.63 0.002 AKR1C1 0.660.003 0.63 <.001 AKT3 0.68 0.006 0.77 0.010 ALDH1A2 0.28 <.001 0.33<.001 ALKBH3 0.77 0.040 0.77 0.029 AMPD3 0.67 0.007 ANPEP 0.68 0.0080.59 <.001 ANXA2 0.72 0.018 APC 0.69 0.002 AXIN2 0.46 <.001 0.54 <.001AZGP1 0.52 <.001 0.53 <.001 BIK 0.69 0.006 0.73 0.003 BIN1 0.43 <.0010.61 <.001 BTG3 0.79 0.030 BTRC 0.48 <.001 0.62 <.001 C7 0.37 <.001 0.55<.001 CADM1 0.56 <.001 0.69 0.001 CAV1 0.58 0.002 0.70 0.009 CAV2 0.650.029 CCNH 0.67 0.006 0.77 0.048 CD164 0.59 0.003 0.57 <.001 CDC25B 0.770.035 CDH1 0.66 <.001 CDK2 0.71 0.003 CDKN1C 0.58 <.001 0.57 <.001 CDS20.69 0.002 CHN1 0.66 0.002 COL6A1 0.44 <.001 0.66 <.001 COL6A3 0.660.006 CSRP1 0.42 0.006 CTGF 0.74 0.043 CTNNA1 0.70 <.001 0.83 0.018CTNNB1 0.70 0.019 CTNND1 0.75 0.028 CUL1 0.74 0.011 CXCL12 0.54 <.0010.74 0.006 CYP3A5 0.52 <.001 0.66 0.003 CYR61 0.64 0.004 0.68 0.005 DDR20.57 0.002 0.73 0.004 DES 0.34 <.001 0.58 <.001 DLGAP1 0.54 <.001 0.62<.001 DNM3 0.67 0.004 DPP4 0.41 <.001 0.53 <.001 DPT 0.28 <.001 0.48<.001 DUSP1 0.59 <.001 0.63 <.001 EDNRA 0.64 0.004 0.74 0.008 EGF 0.710.012 EGR1 0.59 <.001 0.67 0.009 EGR3 0.72 0.026 0.71 0.025 EIF5 0.760.025 ELK4 0.58 0.001 0.70 0.008 ENPP2 0.66 0.002 0.70 0.005 EPHA3 0.650.006 EPHB2 0.60 <.001 0.78 0.023 EPHB4 0.75 0.046 0.73 0.006 ERBB3 0.760.040 0.75 0.013 ERBB4 0.74 0.023 ERCC1 0.63 <.001 0.77 0.016 FAAH 0.670.003 0.71 0.010 FAM107A 0.35 <.001 0.59 <.001 FAM13C 0.37 <.001 0.48<.001 FAS 0.73 0.019 0.72 0.008 FGF10 0.53 <.001 0.58 <.001 FGF7 0.52<.001 0.59 <.001 FGFR2 0.60 <.001 0.59 <.001 FKBP5 0.70 0.039 0.68 0.003FLNA 0.39 <.001 0.56 <.001 FLNC 0.33 <.001 0.52 <.001 FOS 0.58 <.0010.66 0.005 FOXO1 0.57 <.001 0.67 <.001 FOXQ1 0.74 0.023 GADD45B 0.620.002 0.71 0.010 GHR 0.62 0.002 0.72 0.009 GNRH1 0.74 0.049 0.75 0.026GPM6B 0.48 <.001 0.68 <.001 GPS1 0.68 0.003 GSN 0.46 <.001 0.77 0.027GSTM1 0.44 <.001 0.62 <.001 GSTM2 0.29 <.001 0.49 <.001 HGD 0.77 0.020HIRIP3 0.75 0.034 HK1 0.48 <.001 0.66 0.001 HLF 0.42 <.001 0.55 <.001HNF1B 0.67 0.006 0.74 0.010 HPS1 0.66 0.001 0.65 <.001 HSP90AB1 0.750.042 HSPA5 0.70 0.011 HSPB2 0.52 <.001 0.70 0.004 IGF1 0.35 <.001 0.59<.001 IGF2 0.48 <.001 0.70 0.005 IGFBP2 0.61 <.001 0.77 0.044 IGFBP50.63 <.001 IGFBP6 0.45 <.001 0.64 <.001 IL6ST 0.55 0.004 0.63 <.001 ILK0.40 <.001 0.57 <.001 ING5 0.56 <.001 0.78 0.033 ITGA1 0.56 0.004 0.61<.001 ITGA3 0.78 0.035 ITGA5 0.71 0.019 0.75 0.017 ITGA7 0.37 <.001 0.52<.001 ITGB3 0.63 0.003 0.70 0.005 ITPR1 0.46 <.001 0.64 <.001 ITPR3 0.700.013 ITSN1 0.62 0.001 JUN 0.48 <.001 0.60 <.001 JUNB 0.72 0.025 KIT0.51 <.001 0.68 0.007 KLC1 0.58 <.001 KLK1 0.69 0.028 0.66 0.003 KLK20.60 <.001 KLK3 0.63 <.001 0.69 0.012 KRT15 0.56 <.001 0.60 <.001 KRT180.74 0.034 KRT5 0.64 <.001 0.62 <.001 LAMA4 0.47 <.001 0.73 0.010 LAMB30.73 0.018 0.69 0.003 LGALS3 0.59 0.003 0.54 <.001 LIG3 0.75 0.044MAP3K7 0.66 0.003 0.79 0.031 MCM3 0.73 0.013 0.80 0.034 MGMT 0.61 0.0010.71 0.007 MGST1 0.75 0.017 MLXIP 0.70 0.013 MMP2 0.57 <.001 0.72 0.010MMP7 0.69 0.009 MPPED2 0.70 0.009 0.59 <.001 MSH6 0.78 0.046 MTA1 0.690.007 MTSS1 0.55 <.001 0.54 <.001 MYBPC1 0.45 <.001 0.45 <.001 NCAM10.51 <.001 0.65 <.001 NCAPD3 0.42 <.001 0.53 <.001 NCOR2 0.68 0.002NDUFS5 0.66 0.001 0.70 0.013 NEXN 0.48 <.001 0.62 <.001 NFAT5 0.55 <.0010.67 0.001 NFKBIA 0.79 0.048 NRG1 0.58 0.001 0.62 0.001 OLFML3 0.42<.001 0.58 <.001 OMD 0.67 0.004 0.71 0.004 OR51E2 0.65 <.001 0.76 0.007PAGE4 0.27 <.001 0.46 <.001 PCA3 0.68 0.004 PCDHGB7 0.70 0.025 0.65<.001 PGF 0.62 0.001 PGR 0.63 0.028 PHTF2 0.69 0.033 PLP2 0.54 <.0010.71 0.003 PPAP2B 0.41 <.001 0.54 <.001 PPP1R12A 0.48 <.001 0.60 <.001PRIMA1 0.62 0.003 0.65 <.001 PRKAR1B 0.70 0.009 PRKAR2B 0.79 0.038 PRKCA0.37 <.001 0.55 <.001 PRKCB 0.47 <.001 0.56 <.001 PTCH1 0.70 0.021 PTEN0.66 0.010 0.64 <.001 PTGER3 0.76 0.015 PTGS2 0.70 0.013 0.68 0.005PTH1R 0.48 <.001 PTK2B 0.67 0.014 0.69 0.002 PYCARD 0.72 0.023 RAB27A0.76 0.017 RAGE 0.77 0.040 0.57 <.001 RARB 0.66 0.002 0.69 0.002 RECK0.65 <.001 RHOA 0.73 0.043 RHOB 0.61 0.005 0.62 <.001 RND3 0.63 0.0060.66 <.001 SDHC 0.69 0.002 SEC23A 0.61 <.001 0.74 0.010 SEMA3A 0.49<.001 0.55 <.001 SERPINA3 0.70 0.034 0.75 0.020 SH3RF2 0.33 <.001 0.42<.001 SLC22A3 0.23 <.001 0.37 <.001 SMAD4 0.33 <.001 0.39 <.001 SMARCC20.62 0.003 0.74 0.008 SMO 0.53 <.001 0.73 0.009 SORBS1 0.40 <.001 0.55<.001 SPARCL1 0.42 <.001 0.63 <.001 SRD5A2 0.28 <.001 0.37 <.001 ST50.52 <.001 0.63 <.001 STAT5A 0.60 <.001 0.75 0.020 STAT5B 0.54 <.0010.65 <.001 STS 0.78 0.035 SUMO1 0.75 0.017 0.71 0.002 SVIL 0.45 <.0010.62 <.001 TARP 0.72 0.017 TGFB1I1 0.37 <.001 0.53 <.001 TGFB2 0.610.025 0.59 <.001 TGFB3 0.46 <.001 0.60 <.001 TIMP2 0.62 0.001 TIMP3 0.55<.001 0.76 0.019 TMPRSS2 0.71 0.014 TNF 0.65 0.010 TNFRSF10A 0.71 0.0140.74 0.010 TNFRSF10B 0.74 0.030 0.73 0.016 TNFSF10 0.69 0.004 TP53 0.730.011 TP63 0.62 <.001 0.68 0.003 TPM1 0.43 <.001 0.47 <.001 TPM2 0.30<.001 0.47 <.001 TPP2 0.58 <.001 0.69 0.001 TRA2A 0.71 0.006 TRAF3IP20.50 <.001 0.63 <.001 TRO 0.40 <.001 0.59 <.001 TRPC6 0.73 0.030 TRPV60.80 0.047 VCL 0.44 <.001 0.55 <.001 VEGFB 0.73 0.029 VIM 0.72 0.013VTI1B 0.78 0.046 WDR19 0.65 <.001 WFDC1 0.50 <.001 0.72 0.010 YY1 0.750.045 ZFHX3 0.52 <.001 0.54 <.001 ZFP36 0.65 0.004 0.69 0.012 ZNF8270.59 <.001 0.69 0.004

To identify genes associated with recurrence (cRFI, bRFI) in the primaryand the highest Gleason pattern, each of 727 genes were analyzed inunivariate models using specimens A1 and B2 (see Table 2, above). Tables4A and 4B provide genes that were associated, positively or negatively,with cRFI and/or bRFI in the primary and/or highest Gleason pattern.Increased expression of genes in Table 4A is negatively associated withgood prognosis, while increased expression of genes in Table 4B ispositively associated with good prognosis.

TABLE 4A Table 4A. Genes significantly (p < 0.05) associated with cRFIor bRFI in the primary Gleason pattern or highest Gleason pattern withhazard ratio (HR) > 1.0 (increased expression is negatively associatedwith good prognosis) cRFI cRFI bRFI bRFI Primary Highest Primary HighestPattern Pattern Pattern Pattern Official p- p- p- p- Symbol HR value HRvalue HR value HR value AKR1C3 1.304 0.022 1.312 0.013 ANLN 1.379 0.0021.579 <.001 1.465 <.001 1.623 <.001 AQP2 1.184 0.027 1.276 <.001 ASAP21.442 0.006 ASPN 2.272 <.001 2.106 <.001 1.861 <.001 1.895 <.001 ATP5E1.414 0.013 1.538 <.001 BAG5 1.263 0.044 BAX 1.332 0.026 1.327 0.0121.438 0.002 BGN 1.947 <.001 2.061 <.001 1.339 0.017 BIRC5 1.497 <.0011.567 <.001 1.478 <.001 1.575 <.001 BMP6 1.705 <.001 2.016 <.001 1.4180.004 1.541 <.001 BMPR1B 1.401 0.013 1.325 0.016 BRCA2 1.259 0.007 BUB11.411 <.001 1.435 <.001 1.352 <.001 1.242 0.002 CADPS 1.387 0.009 1.2940.027 CCNB1 1.296 0.016 1.376 0.002 CCNE2 1.468 <.001 1.649 <.001 1.729<.001 1.563 <.001 CD276 1.678 <.001 1.832 <.001 1.581 <.001 1.385 0.002CDC20 1.547 <.001 1.671 <.001 1.446 <.001 1.540 <.001 CDC6 1.400 0.0031.290 0.030 1.403 0.002 1.276 0.019 CDH7 1.403 0.003 1.413 0.002 CDKN2B1.569 <.001 1.752 <.001 1.333 0.017 1.347 0.006 CDKN2C 1.612 <.001 1.780<.001 1.323 0.005 1.335 0.004 CDKN3 1.384 <.001 1.255 0.024 1.285 0.0031.216 0.028 CENPF 1.578 <.001 1.692 <.001 1.740 <.001 1.705 <.001 CKS21.390 0.007 1.418 0.005 1.291 0.018 CLTC 1.368 0.045 COL1A1 1.873 <.0012.103 <.001 1.491 <.001 1.472 <.001 COL1A2 1.462 0.001 COL3A1 1.827<.001 2.005 <.001 1.302 0.012 1.298 0.018 COL4A1 1.490 0.002 1.613 <.001COL8A1 1.692 <.001 1.926 <.001 1.307 0.013 1.317 0.010 CRISP3 1.4250.001 1.467 <.001 1.242 0.045 CTHRC1 1.505 0.002 2.025 <.001 1.425 0.0031.369 0.005 CTNND2 1.412 0.003 CXCR4 1.312 0.023 1.355 0.008 DDIT4 1.543<.001 1.763 <.001 DYNLL1 1.290 0.039 1.201 0.004 EIF3H 1.428 0.012 ENY21.361 0.014 1.392 0.008 1.371 0.001 EZH2 1.311 0.010 F2R 1.773 <.0011.695 <.001 1.495 <.001 1.277 0.018 FADD 1.292 0.018 FAM171B 1.285 0.036FAP 1.455 0.004 1.560 0.001 1.298 0.022 1.274 0.038 FASN 1.263 0.035FCGR3A 1.654 <.001 1.253 0.033 1.350 0.007 FGF5 1.219 0.030 GNPTAB 1.3880.007 1.503 0.003 1.355 0.005 1.434 0.002 GPR68 1.361 0.008 GREM1 1.4700.003 1.716 <.001 1.421 0.003 1.316 0.017 HDAC1 1.290 0.025 HDAC9 1.3950.012 HRAS 1.424 0.006 1.447 0.020 HSD17B4 1.342 0.019 1.282 0.026 1.569<.001 1.390 0.002 HSPA8 1.290 0.034 IGFBP3 1.333 0.022 1.442 0.003 1.2530.040 1.323 0.005 INHBA 2.368 <.001 2.765 <.001 1.466 0.002 1.671 <.001JAG1 1.359 0.006 1.367 0.005 1.259 0.024 KCNN2 1.361 0.011 1.413 0.0051.312 0.017 1.281 0.030 KHDRBS3 1.387 0.006 1.601 <.001 1.573 <.0011.353 0.006 KIAA0196 1.249 0.037 KIF4A 1.212 0.016 1.149 0.040 1.2780.003 KLK14 1.167 0.023 1.180 0.007 KPNA2 1.425 0.009 1.353 0.005 1.3050.019 KRT75 1.164 0.028 LAMA3 1.327 0.011 LAMB1 1.347 0.019 LAMC1 1.5550.001 1.310 0.030 1.349 0.014 LIMS1 1.275 0.022 LOX 1.358 0.003 1.410<.001 LTBP2 1.396 0.009 1.656 <.001 1.278 0.022 LUM 1.315 0.021 MANF1.660 <.001 1.323 0.011 MCM2 1.345 0.011 1.387 0.014 MCM6 1.307 0.0231.352 0.008 1.244 0.039 MELK 1.293 0.014 1.401 <.001 1.501 <.001 1.2560.012 MMP11 1.680 <.001 1.474 <.001 1.489 <.001 1.257 0.030 MRPL13 1.2600.025 MSH2 1.295 0.027 MYBL2 1.664 <.001 1.670 <.001 1.399 <.001 1.431<.001 MYO6 1.301 0.033 NETO2 1.412 0.004 1.302 0.027 1.298 0.009 NFKB11.236 0.050 NOX4 1.492 <.001 1.507 0.001 1.555 <.001 1.262 0.019 NPM11.287 0.036 NRIP3 1.219 0.031 1.218 0.018 NRP1 1.482 0.002 1.245 0.041OLFML2B 1.362 0.015 OR51E1 1.531 <.001 1.488 0.003 PAK6 1.269 0.033PATE1 1.308 <.001 1.332 <.001 1.164 0.044 PCNA 1.278 0.020 PEX10 1.4360.005 1.393 0.009 PGD 1.298 0.048 1.579 <.001 PGK1 1.274 0.023 1.2620.009 PLA2G7 1.315 0.011 1.346 0.005 PLAU 1.319 0.010 PLK1 1.309 0.0211.563 <.001 1.410 0.002 1.372 0.003 PLOD2 1.284 0.019 1.272 0.014 1.3320.005 POSTN 1.599 <.001 1.514 0.002 1.391 0.005 PPP3CA 1.402 0.007 1.3160.018 PSMD13 1.278 0.040 1.297 0.033 1.279 0.017 1.373 0.004 PTK6 1.640<.001 1.932 <.001 1.369 0.001 1.406 <.001 PTTG1 1.409 <.001 1.510 <.0011.347 0.001 1.558 <.001 RAD21 1.315 0.035 1.402 0.004 1.589 <.001 1.439<.001 RAF1 1.503 0.002 RALA 1.521 0.004 1.403 0.007 1.563 <.001 1.2290.040 RALBP1 1.277 0.033 RGS7 1.154 0.015 1.266 0.010 RRM1 1.570 0.0011.602 <.001 RRM2 1.368 <.001 1.289 0.004 1.396 <.001 1.230 0.015 SAT11.482 0.016 1.403 0.030 SDC1 1.340 0.018 1.396 0.018 SEC14L1 1.260 0.0481.360 0.002 SESN3 1.485 <.001 1.631 <.001 1.232 0.047 1.292 0.014 SFRP41.800 <.001 1.814 <.001 1.496 <.001 1.289 0.027 SHMT2 1.807 <.001 1.658<.001 1.673 <.001 1.548 <.001 SKIL 1.327 0.008 SLC25A21 1.398 0.0011.285 0.018 SOX4 1.286 0.020 1.280 0.030 SPARC 1.539 <.001 1.842 <.0011.269 0.026 SPP1 1.322 0.022 SQLE 1.359 0.020 1.270 0.036 STMN1 1.4020.007 1.446 0.005 1.279 0.031 SULF1 1.587 <.001 TAF2 1.273 0.027 TFDP11.328 0.021 1.400 0.005 1.416 0.001 THBS2 1.812 <.001 1.960 <.001 1.3200.012 1.256 0.038 THY1 1.362 0.020 1.662 <.001 TK1 1.251 0.011 1.377<.001 1.401 <.001 TOP2A 1.670 <.001 1.920 <.001 1.869 <.001 1.927 <.001TPD52 1.324 0.011 1.366 0.002 1.351 0.005 TPX2 1.884 <.001 2.154 <.0011.874 <.001 1.794 <.001 UAP1 1.244 0.044 UBE2C 1.403 <.001 1.541 <.0011.306 0.002 1.323 <.001 UBE2T 1.667 <.001 1.282 0.023 1.502 <.001 1.2980.005 UGT2B15 1.295 0.001 1.275 0.002 UGT2B17 1.294 0.025 UHRF1 1.454<.001 1.531 <.001 1.257 0.029 VCPIP1 1.390 0.009 1.414 0.004 1.294 0.0211.283 0.021 WNT5A 1.274 0.038 1.298 0.020 XIAP 1.464 0.006 ZMYND8 1.2770.048 ZWINT 1.259 0.047

TABLE 4B Table 4B. Genes significantly (p < 0.05) associated with cRFIor bRFI in the primary Gleason pattern or highest Gleason pattern withhazard ratio (HR) < 1.0 (increased expression is positively associatedwith good prognosis) cRFI cRFI bRFI bRFI Primary Highest Primary HighestPattern Pattern Pattern Pattern Official p- p- p- p- Symbol HR value HRvalue HR value HR value AAMP 0.564 <.001 0.571 <.001 0.764 0.037 0.7860.034 ABCA5 0.755 <.001 0.695 <.001 0.800 0.006 ABCB1 0.777 0.026 ABCG20.788 0.033 0.784 0.040 0.803 0.018 0.750 0.004 ABHD2 0.734 0.011 ACE0.782 0.048 ACOX2 0.639 <.001 0.631 <.001 0.713 <.001 0.716 0.002 ADH50.625 <.001 0.637 <.001 0.753 0.026 AKAP1 0.764 0.006 0.800 0.005 0.8370.046 AKR1C1 0.773 0.033 0.802 0.032 AKT1 0.714 0.005 AKT3 0.811 0.0150.809 0.021 ALDH1A2 0.606 <.001 0.498 <.001 0.613 <.001 0.624 <.001AMPD3 0.793 0.024 ANPEP 0.584 <.001 0.493 <.001 ANXA2 0.753 0.013 0.7810.036 0.762 0.008 0.795 0.032 APRT 0.758 0.026 0.780 0.044 0.746 0.008ATXN1 0.673 0.001 0.776 0.029 0.809 0.031 0.812 0.043 AXIN2 0.674 <.0010.571 <.001 0.776 0.005 0.757 0.005 AZGP1 0.585 <.001 0.652 <.001 0.664<.001 0.746 <.001 BAD 0.765 0.023 BCL2 0.788 0.033 0.778 0.036 BDKRB10.728 0.039 BIK 0.712 0.005 BIN1 0.607 <.001 0.724 0.002 0.726 <.0010.834 0.034 BTG3 0.847 0.034 BTRC 0.688 0.001 0.713 0.003 C7 0.589 <.0010.639 <.001 0.629 <.001 0.691 <.001 CADM1 0.546 <.001 0.529 <.001 0.7430.008 0.769 0.015 CASP1 0.769 0.014 0.799 0.028 0.799 0.010 0.815 0.018CAV1 0.736 0.011 0.711 0.005 0.675 <.001 0.743 0.006 CAV2 0.636 0.0100.648 0.012 0.685 0.012 CCL2 0.759 0.029 0.764 0.024 CCNH 0.689 <.0010.700 <.001 CD164 0.664 <.001 0.651 <.001 CD1A 0.687 0.004 CD44 0.545<.001 0.600 <.001 0.788 0.018 0.799 0.023 CD82 0.771 0.009 0.748 0.004CDC25B 0.755 0.006 0.817 0.025 CDK14 0.845 0.043 CDK2 0.819 0.032 CDK30.733 0.005 0.772 0.006 0.838 0.017 CDKN1A 0.766 0.041 CDKN1C 0.662<.001 0.712 0.002 0.693 <.001 0.761 0.009 CHN1 0.788 0.036 COL6A1 0.608<.001 0.767 0.013 0.706 <.001 0.775 0.007 CSF1 0.626 <.001 0.709 0.003CSK 0.837 0.029 CSRP1 0.793 0.024 0.782 0.019 CTNNB1 0.898 0.042 0.885<.001 CTSB 0.701 0.004 0.713 0.007 0.715 0.002 0.803 0.038 CTSK 0.8150.042 CXCL12 0.652 <.001 0.802 0.044 0.711 0.001 CYP3A5 0.463 <.0010.436 <.001 0.727 0.003 CYR61 0.652 0.002 0.676 0.002 DAP 0.761 0.0260.775 0.025 0.802 0.048 DARC 0.725 0.005 0.792 0.032 DDR2 0.719 0.0010.763 0.008 DES 0.619 <.001 0.737 0.005 0.638 <.001 0.793 0.017 DHRS90.642 0.003 DHX9 0.888 <.001 DLC1 0.710 0.007 0.715 0.009 DLGAP1 0.613<.001 0.551 <.001 0.779 0.049 DNM3 0.679 <.001 0.812 0.037 DPP4 0.591<.001 0.613 <.001 0.761 0.003 DPT 0.613 <.001 0.576 <.001 0.647 <.0010.677 <.001 DUSP1 0.662 0.001 0.665 0.001 0.785 0.024 DUSP6 0.713 0.0050.668 0.002 EDNRA 0.702 0.002 0.779 0.036 EGF 0.738 0.028 EGR1 0.569<.001 0.577 <.001 0.782 0.022 EGR3 0.601 <.001 0.619 <.001 0.800 0.038EIF2S3 0.756 0.015 EIF5 0.776 0.023 0.787 0.028 ELK4 0.628 <.001 0.658<.001 EPHA2 0.720 0.011 0.663 0.004 EPHA3 0.727 0.003 0.772 0.005 ERBB20.786 0.019 0.738 0.003 0.815 0.041 ERBB3 0.728 0.002 0.711 0.002 0.8280.043 0.813 0.023 ERCC1 0.771 0.023 0.725 0.007 0.806 0.049 0.704 0.002EREG 0.754 0.016 0.777 0.034 ESR2 0.731 0.026 FAAH 0.708 0.004 0.7580.012 0.784 0.031 0.774 0.007 FAM107A 0.517 <.001 0.576 <.001 0.642<.001 0.656 <.001 FAM13C 0.568 <.001 0.526 <.001 0.739 0.002 0.639 <.001FAS 0.755 0.014 FASLG 0.706 0.021 FGF10 0.653 <.001 0.685 <.001 0.7660.022 FGF17 0.746 0.023 0.781 0.015 0.805 0.028 FGF7 0.794 0.030 0.8200.037 0.811 0.040 FGFR2 0.683 <.001 0.686 <.001 0.674 <.001 0.703 <.001FKBP5 0.676 0.001 FLNA 0.653 <.001 0.741 0.010 0.682 <.001 0.771 0.016FLNC 0.751 0.029 0.779 0.047 0.663 <.001 0.725 <.001 FLT1 0.799 0.044FOS 0.566 <.001 0.543 <.001 0.757 0.006 FOXO1 0.816 0.039 0.798 0.023FOXQ1 0.753 0.017 0.757 0.024 0.804 0.018 FYN 0.779 0.031 GADD45B 0.590<.001 0.619 <.001 GDF15 0.759 0.019 0.794 0.048 GHR 0.702 0.005 0.630<.001 0.673 <.001 0.590 <.001 GNRH1 0.742 0.014 GPM6B 0.653 <.001 0.633<.001 0.696 <.001 0.768 0.007 GSN 0.570 <.001 0.697 0.001 0.697 <.0010.758 0.005 GSTM1 0.612 <.001 0.588 <.001 0.718 <.001 0.801 0.020 GSTM20.540 <.001 0.630 <.001 0.602 <.001 0.706 <.001 HGD 0.796 0.020 0.7360.002 HIRIP3 0.753 0.011 0.824 0.050 HK1 0.684 <.001 0.683 <.001 0.7990.011 0.804 0.014 HLA-G 0.726 0.022 HLF 0.555 <.001 0.582 <.001 0.703<.001 0.702 <.001 HNF1B 0.690 <.001 0.585 <.001 HPS1 0.744 0.003 0.7840.020 0.836 0.047 HSD3B2 0.733 0.016 HSP90AB1 0.801 0.036 HSPA5 0.7760.034 HSPB1 0.813 0.020 HSPB2 0.762 0.037 0.699 0.002 0.783 0.034 HSPG20.794 0.044 ICAM1 0.743 0.024 0.768 0.040 IER3 0.686 0.002 0.663 <.001IFIT1 0.649 <.001 0.761 0.026 IGF1 0.634 <.001 0.537 <.001 0.696 <.0010.688 <.001 IGF2 0.732 0.004 IGFBP2 0.548 <.001 0.620 <.001 IGFBP5 0.681<.001 IGFBP6 0.577 <.001 0.675 <.001 IL1B 0.712 0.005 0.742 0.009 IL60.763 0.028 IL6R 0.791 0.039 IL6ST 0.585 <.001 0.639 <.001 0.730 0.0020.768 0.006 IL8 0.624 <.001 0.662 0.001 ILK 0.712 0.009 0.728 0.0120.790 0.047 0.790 0.042 ING5 0.625 <.001 0.658 <.001 0.728 0.002 ITGA50.728 0.006 0.803 0.039 ITGA6 0.779 0.007 0.775 0.006 ITGA7 0.584 <.0010.700 0.001 0.656 <.001 0.786 0.014 ITGAD 0.657 0.020 ITGB4 0.718 0.0070.689 <.001 0.818 0.041 ITGB5 0.801 0.050 ITPR1 0.707 0.001 JUN 0.556<.001 0.574 <.001 0.754 0.008 JUNB 0.730 0.017 0.715 0.010 KIT 0.6440.004 0.705 0.019 0.605 <.001 0.659 0.001 KLC1 0.692 0.003 0.774 0.0240.747 0.008 KLF6 0.770 0.032 0.776 0.039 KLK1 0.646 <.001 0.652 0.0010.784 0.037 KLK10 0.716 0.006 KLK2 0.647 <.001 0.628 <.001 0.786 0.009KLK3 0.706 <.001 0.748 <.001 0.845 0.018 KRT1 0.734 0.024 KRT15 0.627<.001 0.526 <.001 0.704 <.001 0.782 0.029 KRT18 0.624 <.001 0.617 <.0010.738 0.005 0.760 0.005 KRT5 0.640 <.001 0.550 <.001 0.740 <.001 0.7980.023 KRT8 0.716 0.006 0.744 0.008 L1CAM 0.738 0.021 0.692 0.009 0.7610.036 LAG3 0.741 0.013 0.729 0.011 LAMA4 0.686 0.011 0.592 0.003 LAMA50.786 0.025 LAMB3 0.661 <.001 0.617 <.001 0.734 <.001 LGALS3 0.618 <.0010.702 0.001 0.734 0.001 0.793 0.012 LIG3 0.705 0.008 0.615 <.001 LRP10.786 0.050 0.795 0.023 0.770 0.009 MAP3K7 0.789 0.003 MGMT 0.632 <.0010.693 <.001 MICA 0.781 0.014 0.653 <.001 0.833 0.043 MPPED2 0.655 <.0010.597 <.001 0.719 <.001 0.759 0.006 MSH6 0.793 0.015 MTSS1 0.613 <.0010.746 0.008 MVP 0.792 0.028 0.795 0.045 0.819 0.023 MYBPC1 0.648 <.0010.496 <.001 0.701 <.001 0.629 <.001 NCAM1 0.773 0.015 NCAPD3 0.574 <.0010.463 <.001 0.679 <.001 0.640 <.001 NEXN 0.701 0.002 0.791 0.035 0.7250.002 0.781 0.016 NFAT5 0.515 <.001 0.586 <.001 0.785 0.017 NFATC2 0.7530.023 NFKBIA 0.778 0.037 NRG1 0.644 0.004 0.696 0.017 0.698 0.012 OAZ10.777 0.034 0.775 0.022 OLFML3 0.621 <.001 0.720 0.001 0.600 <.001 0.626<.001 OMD 0.706 0.003 OR51E2 0.820 0.037 0.798 0.027 PAGE4 0.549 <.0010.613 <.001 0.542 <.001 0.628 <.001 PCA3 0.684 <.001 0.635 <.001 PCDHGB70.790 0.045 0.725 0.002 0.664 <.001 PGF 0.753 0.017 PGR 0.740 0.0210.728 0.018 PIK3CG 0.803 0.024 PLAUR 0.778 0.035 PLG 0.728 0.028 PPAP2B0.575 <.001 0.629 <.001 0.643 <.001 0.699 <.001 PPP1R12A 0.647 <.0010.683 0.002 0.782 0.023 0.784 0.030 PRIMA1 0.626 <.001 0.658 <.001 0.7030.002 0.724 0.003 PRKCA 0.642 <.001 0.799 0.029 0.677 0.001 0.776 0.006PRKCB 0.675 0.001 0.648 <.001 0.747 0.006 PROM1 0.603 0.018 0.659 0.0140.493 0.008 PTCH1 0.680 0.001 0.753 0.010 0.789 0.018 PTEN 0.732 0.0020.747 0.005 0.744 <.001 0.765 0.002 PTGS2 0.596 <.001 0.610 <.001 PTH1R0.767 0.042 0.775 0.028 0.788 0.047 PTHLH 0.617 0.002 0.726 0.025 0.6680.002 0.718 0.007 PTK2B 0.744 0.003 0.679 <.001 0.766 0.002 0.726 <.001PTPN1 0.760 0.020 0.780 0.042 PYCARD 0.748 0.012 RAB27A 0.708 0.004RAB30 0.755 0.008 RAGE 0.817 0.048 RAP1B 0.818 0.050 RARB 0.757 0.0070.677 <.001 0.789 0.007 0.746 0.003 RASSF1 0.816 0.035 RHOB 0.725 0.0090.676 0.001 0.793 0.039 RLN1 0.742 0.033 0.762 0.040 RND3 0.636 <.0010.647 <.001 RNF114 0.749 0.011 SDC2 0.721 0.004 SDHC 0.725 0.003 0.7270.006 SEMA3A 0.757 0.024 0.721 0.010 SERPINA3 0.716 0.008 0.660 0.001SERPINB5 0.747 0.031 0.616 0.002 SH3RF2 0.577 <.001 0.458 <.001 0.702<.001 0.640 <.001 SLC22A3 0.565 <.001 0.540 <.001 0.747 0.004 0.7560.007 SMAD4 0.546 <.001 0.573 <.001 0.636 <.001 0.627 <.001 SMARCD10.718 <.001 0.775 0.017 SMO 0.793 0.029 0.754 0.021 0.718 0.003 SOD10.757 0.049 0.707 0.006 SORBS1 0.645 <.001 0.716 0.003 0.693 <.001 0.7840.025 SPARCL1 0.821 0.028 0.829 0.014 0.781 0.030 SPDEF 0.778 <.001SPINT1 0.732 0.009 0.842 0.026 SRC 0.647 <.001 0.632 <.001 SRD5A1 0.8130.040 SRD5A2 0.489 <.001 0.533 <.001 0.544 <.001 0.611 <.001 ST5 0.7130.002 0.783 0.011 0.725 <.001 0.827 0.025 STAT3 0.773 0.037 0.759 0.035STAT5A 0.695 <.001 0.719 0.002 0.806 0.020 0.783 0.008 STAT5B 0.633<.001 0.655 <.001 0.814 0.028 SUMO1 0.790 0.015 SVIL 0.659 <.001 0.7130.002 0.711 0.002 0.779 0.010 TARP 0.800 0.040 TBP 0.761 0.010 TFF30.734 0.010 0.659 <.001 TGFB1I1 0.618 <.001 0.693 0.002 0.637 <.0010.719 0.004 TGFB2 0.679 <.001 0.747 0.005 0.805 0.030 TGFB3 0.791 0.037TGFBR2 0.778 0.035 TIMP3 0.751 0.011 TMPRSS2 0.745 0.003 0.708 <.001 TNF0.670 0.013 0.697 0.015 TNFRSF10A 0.780 0.018 0.752 0.006 0.817 0.032TNFRSF10B 0.576 <.001 0.655 <.001 0.766 0.004 0.778 0.002 TNFRSF18 0.6480.016 0.759 0.034 TNFSF10 0.653 <.001 0.667 0.004 TP53 0.729 0.003 TP630.759 0.016 0.636 <.001 0.698 <.001 0.712 0.001 TPM1 0.778 0.048 0.7430.012 0.783 0.032 0.811 0.046 TPM2 0.578 <.001 0.634 <.001 0.611 <.0010.710 0.001 TPP2 0.775 0.037 TRAF3IP2 0.722 0.002 0.690 <.001 0.7920.021 0.823 0.049 TRO 0.744 0.003 0.725 0.003 0.765 0.002 0.821 0.041TUBB2A 0.639 <.001 0.625 <.001 TYMP 0.786 0.039 VCL 0.594 <.001 0.6570.001 0.682 <.001 VEGFA 0.762 0.024 VEGFB 0.795 0.037 VIM 0.739 0.0090.791 0.021 WDR19 0.776 0.015 WFDC1 0.746 <.001 YY1 0.683 0.001 0.7280.002 ZFHX3 0.684 <.001 0.661 <.001 0.801 0.010 0.762 0.001 ZFP36 0.605<.001 0.579 <.001 0.815 0.043 ZNF827 0.624 <.001 0.730 0.007 0.738 0.004

Tables 5A and 5B provide genes that were significantly associated(p<0.05), positively or negatively, with recurrence (cRFI, bRFI) afteradjusting for AUA risk group in the primary and/or highest Gleasonpattern. Increased expression of genes in Table 5A is negativelyassociated with good prognosis, while increased expression of genes inTable 5B is positively associated with good prognosis.

TABLE 5A Table 5A. Gene significantly (p < 0.05) associated with cRFI orbRFI after adjustment for AUA risk group in the primary Gleason patternor highest Gleason pattern with hazard ratio (HR) > 1.0 (increasedexpression negatively associated with good prognosis) cRFI cRFI bRFIbRFI Primary Highest Primary Highest Pattern Pattern Pattern PatternOfficial p- p- p- p- Symbol HR value HR value HR value HR value AKR1C31.315 0.018 1.283 0.024 ALOX12 1.198 0.024 ANLN 1.406 <.001 1.519 <.0011.485 <.001 1.632 <.001 AQP2 1.209 <.001 1.302 <.001 ASAP2 1.582 <.0011.333 0.011 1.307 0.019 ASPN 1.872 <.001 1.741 <.001 1.638 <.001 1.691<.001 ATP5E 1.309 0.042 1.369 0.012 BAG5 1.291 0.044 BAX 1.298 0.0251.420 0.004 BGN 1.746 <.001 1.755 <.001 BIRC5 1.480 <.001 1.470 <.0011.419 <.001 1.503 <.001 BMP6 1.536 <.001 1.815 <.001 1.294 0.033 1.4290.001 BRCA2 1.184 0.037 BUB1 1.288 0.001 1.391 <.001 1.254 <.001 1.1890.018 CACNA1D 1.313 0.029 CADPS 1.358 0.007 1.267 0.022 CASP3 1.2510.037 CCNB1 1.261 0.033 1.318 0.005 CCNE2 1.345 0.005 1.438 <.001 1.606<.001 1.426 <.001 CD276 1.482 0.002 1.668 <.001 1.451 <.001 1.302 0.011CDC20 1.417 <.001 1.547 <.001 1.355 <.001 1.446 <.001 CDC6 1.340 0.0111.265 0.046 1.367 0.002 1.272 0.025 CDH7 1.402 0.003 1.409 0.002 CDKN2B1.553 <.001 1.746 <.001 1.340 0.014 1.369 0.006 CDKN2C 1.411 <.001 1.604<.001 1.220 0.033 CDKN3 1.296 0.004 1.226 0.015 CENPF 1.434 0.002 1.570<.001 1.633 <.001 1.610 <.001 CKS2 1.419 0.008 1.374 0.022 1.380 0.004COL1A1 1.677 <.001 1.809 <.001 1.401 <.001 1.352 0.003 COL1A2 1.3730.010 COL3A1 1.669 <.001 1.781 <.001 1.249 0.024 1.234 0.047 COL4A11.475 0.002 1.513 0.002 COL8A1 1.506 0.001 1.691 <.001 CRISP3 1.4060.004 1.471 <.001 CTHRC1 1.426 0.009 1.793 <.001 1.311 0.019 CTNND21.462 <.001 DDIT4 1.478 0.003 1.783 <.001 1.236 0.039 DYNLL1 1.431 0.0021.193 0.004 EIF3H 1.372 0.027 ENY2 1.325 0.023 1.270 0.017 ERG 1.3030.041 EZH2 1.254 0.049 F2R 1.540 0.002 1.448 0.006 1.286 0.023 FADD1.235 0.041 1.404 <.001 FAP 1.386 0.015 1.440 0.008 1.253 0.048 FASN1.303 0.028 FCGR3A 1.439 0.011 1.262 0.045 FGF5 1.289 0.006 GNPTAB 1.2900.033 1.369 0.022 1.285 0.018 1.355 0.008 GPR68 1.396 0.005 GREM1 1.3410.022 1.502 0.003 1.366 0.006 HDAC1 1.329 0.016 HDAC9 1.378 0.012 HRAS1.465 0.006 HSD17B4 1.442 <.001 1.245 0.028 IGFBP3 1.366 0.019 1.3020.011 INHBA 2.000 <.001 2.336 <.001 1.486 0.002 JAG1 1.251 0.039 KCNN21.347 0.020 1.524 <.001 1.312 0.023 1.346 0.011 KHDRBS3 1.500 0.0011.426 0.001 1.267 0.032 KIAA0196 1.272 0.028 KIF4A 1.199 0.022 1.2620.004 KPNA2 1.252 0.016 LAMA3 1.332 0.004 1.356 0.010 LAMB1 1.317 0.028LAMC1 1.516 0.003 1.302 0.040 1.397 0.007 LIMS1 1.261 0.027 LOX 1.2650.016 1.372 0.001 LTBP2 1.477 0.002 LUM 1.321 0.020 MANF 1.647 <.0011.284 0.027 MCM2 1.372 0.003 1.302 0.032 MCM3 1.269 0.047 MCM6 1.2760.033 1.245 0.037 MELK 1.294 0.005 1.394 <.001 MKI67 1.253 0.028 1.2460.029 MMP11 1.557 <.001 1.290 0.035 1.357 0.005 MRPL13 1.275 0.003 MSH21.355 0.009 MYBL2 1.497 <.001 1.509 <.001 1.304 0.003 1.292 0.007 MYO61.367 0.010 NDRG1 1.270 0.042 1.314 0.025 NEK2 1.338 0.020 1.269 0.026NETO2 1.434 0.004 1.303 0.033 1.283 0.012 NOX4 1.413 0.006 1.308 0.0371.444 <.001 NRIP3 1.171 0.026 NRP1 1.372 0.020 ODC1 1.450 <.001 OR51E11.559 <.001 1.413 0.008 PAK6 1.233 0.047 PATE1 1.262 <.001 1.375 <.0011.143 0.034 1.191 0.036 PCNA 1.227 0.033 1.318 0.003 PEX10 1.517 <.0011.500 0.001 PGD 1.363 0.028 1.316 0.039 1.652 <.001 PGK1 1.224 0.0341.206 0.024 PIM1 1.205 0.042 PLA2G7 1.298 0.018 1.358 0.005 PLAU 1.2420.032 PLK1 1.464 0.001 1.299 0.018 1.275 0.031 PLOD2 1.206 0.039 1.2610.025 POSTN 1.558 0.001 1.356 0.022 1.363 0.009 PPP3CA 1.445 0.002PSMD13 1.301 0.017 1.411 0.003 PTK2 1.318 0.031 PTK6 1.582 <.001 1.894<.001 1.290 0.011 1.354 0.003 PTTG1 1.319 0.004 1.430 <.001 1.271 0.0061.492 <.001 RAD21 1.278 0.028 1.435 0.004 1.326 0.008 RAF1 1.504 <.001RALA 1.374 0.028 1.459 0.001 RGS7 1.203 0.031 RRM1 1.535 0.001 1.525<.001 RRM2 1.302 0.003 1.197 0.047 1.342 <.001 SAT1 1.374 0.043 SDC11.344 0.011 1.473 0.008 SEC14L1 1.297 0.006 SESN3 1.337 0.002 1.495<.001 1.223 0.038 SFRP4 1.610 <.001 1.542 0.002 1.370 0.009 SHMT2 1.5670.001 1.522 <.001 1.485 0.001 1.370 <.001 SKIL 1.303 0.008 SLC25A211.287 0.020 1.306 0.017 SLC44A1 1.308 0.045 SNRPB2 1.304 0.018 SOX41.252 0.031 SPARC 1.445 0.004 1.706 <.001 1.269 0.026 SPP1 1.376 0.016SQLE 1.417 0.007 1.262 0.035 STAT1 1.209 0.029 STMN1 1.315 0.029 SULF11.504 0.001 TAF2 1.252 0.048 1.301 0.019 TFDP1 1.395 0.010 1.424 0.002THBS2 1.716 <.001 1.719 <.001 THY1 1.343 0.035 1.575 0.001 TK1 1.320<.001 1.304 <.001 TOP2A 1.464 0.001 1.688 <.001 1.715 <.001 1.761 <.001TPD52 1.286 0.006 1.258 0.023 TPX2 1.644 <.001 1.964 <.001 1.699 <.0011.754 <.001 TYMS 1.315 0.014 UBE2C 1.270 0.019 1.558 <.001 1.205 0.0271.333 <.001 UBE2G1 1.302 0.041 UBE2T 1.451 <.001 1.309 0.003 UGT2B151.222 0.025 UHRF1 1.370 0.003 1.520 <.001 1.247 0.020 VCPIP1 1.332 0.015VTI1B 1.237 0.036 XIAP 1.486 0.008 ZMYND8 1.408 0.007 ZNF3 1.284 0.018ZWINT 1.289 0.028

TABLE 5B Table 5B. Genes significantly (p < 0.05) associated with cRFIor bRFI after adjustment for AUA risk group in the primary Gleasonpattern or highest Gleason pattern with hazard ratio (HR) < 1.0(increased expression is positively associated with good prognosis) cRFIcRFI bRFI bRFI Official Primary Pattern Highest Pattern Primary PatternHighest Pattern Symbol HR p-value HR p-value HR p-value HR p-value AAMP0.535 <.001 0.581 <.001 0.700 0.002 0.759 0.006 ABCA5 0.798 0.007 0.7450.002 0.841 0.037 ABCC1 0.800 0.044 ABCC4 0.787 0.022 ABHD2 0.768 0.023ACOX2 0.678 0.002 0.749 0.027 0.759 0.004 ADH5 0.645 <.001 0.672 0.001AGTR1 0.780 0.030 AKAP1 0.815 0.045 0.758 <.001 AKT1 0.732 0.010 ALDH1A20.646 <.001 0.548 <.001 0.671 <.001 0.713 0.001 ANPEP 0.641 <.001 0.535<.001 ANXA2 0.772 0.035 0.804 0.046 ATXN1 0.654 <.001 0.754 0.020 0.7970.017 AURKA 0.788 0.030 AXIN2 0.744 0.005 0.655 <.001 AZGP1 0.656 <.0010.676 <.001 0.754 0.001 0.791 0.004 BAD 0.700 0.004 BIN1 0.650 <.0010.764 0.013 0.803 0.015 BTG3 0.836 0.025 BTRC 0.730 0.005 C7 0.617 <.0010.680 <.001 0.667 <.001 0.755 0.005 CADM1 0.559 <.001 0.566 <.001 0.7720.020 0.802 0.046 CASP1 0.781 0.030 0.779 0.021 0.818 0.027 0.828 0.036CAV1 0.775 0.034 CAV2 0.677 0.019 CCL2 0.752 0.023 CCNH 0.679 <.0010.682 <.001 CD164 0.721 0.002 0.724 0.005 CD1A 0.710 0.014 CD44 0.591<.001 0.642 <.001 CD82 0.779 0.021 0.771 0.024 CDC25B 0.778 0.035 0.8180.023 CDK14 0.788 0.011 CDK3 0.752 0.012 0.779 0.005 0.841 0.020 CDKN1A0.770 0.049 0.712 0.014 CDKN1C 0.684 <.001 0.697 <.001 CHN1 0.772 0.031COL6A1 0.648 <.001 0.807 0.046 0.768 0.004 CSF1 0.621 <.001 0.671 0.001CTNNB1 0.905 0.008 CTSB 0.754 0.030 0.716 0.011 0.756 0.014 CXCL12 0.641<.001 0.796 0.038 0.708 <.001 CYP3A5 0.503 <.001 0.528 <.001 0.791 0.028CYR61 0.639 0.001 0.659 0.001 0.797 0.048 DARC 0.707 0.004 DDR2 0.7500.011 DES 0.657 <.001 0.758 0.022 0.699 <.001 DHRS9 0.625 0.002 DHX90.846 <.001 DIAPH1 0.682 0.007 0.723 0.008 0.780 0.026 DLC1 0.703 0.0050.702 0.008 DLGAP1 0.703 0.008 0.636 <.001 DNM3 0.701 0.001 0.817 0.042DPP4 0.686 <.001 0.716 0.001 DPT 0.636 <.001 0.633 <.001 0.709 0.0060.773 0.024 DUSP1 0.683 0.006 0.679 0.003 DUSP6 0.694 0.003 0.605 <.001EDN1 0.773 0.031 EDNRA 0.716 0.007 EGR1 0.575 <.001 0.575 <.001 0.7710.014 EGR3 0.633 0.002 0.643 <.001 0.792 0.025 EIF4E 0.722 0.002 ELK40.710 0.009 0.759 0.027 ENPP2 0.786 0.039 EPHA2 0.593 0.001 EPHA3 0.7390.006 0.802 0.020 ERBB2 0.753 0.007 ERBB3 0.753 0.009 0.753 0.015 ERCC10.727 0.001 EREG 0.722 0.012 0.769 0.040 ESR1 0.742 0.015 FABP5 0.7560.032 FAM107A 0.524 <.001 0.579 <.001 0.688 <.001 0.699 0.001 FAM13C0.639 <.001 0.601 <.001 0.810 0.019 0.709 <.001 FAS 0.770 0.033 FASLG0.716 0.028 0.683 0.017 FGF10 0.798 0.045 FGF17 0.718 0.018 0.793 0.0240.790 0.024 FGFR2 0.739 0.007 0.783 0.038 0.740 0.004 FGFR4 0.746 0.050FKBP5 0.689 0.003 FLNA 0.701 0.006 0.766 0.029 0.768 0.037 FLNC 0.755<.001 0.820 0.022 FLT1 0.729 0.008 FOS 0.572 <.001 0.536 <.001 0.7500.005 FOXQ1 0.778 0.033 0.820 0.018 FYN 0.708 0.006 GADD45B 0.577 <.0010.589 <.001 GDF15 0.757 0.013 0.743 0.006 GHR 0.712 0.004 0.679 0.001GNRH1 0.791 0.048 GPM6B 0.675 <.001 0.660 <.001 0.735 <.001 0.823 0.049GSK3B 0.783 0.042 GSN 0.587 <.001 0.705 0.002 0.745 0.004 0.796 0.021GSTM1 0.686 0.001 0.631 <.001 0.807 0.018 GSTM2 0.607 <.001 0.683 <.0010.679 <.001 0.800 0.027 HIRIP3 0.692 <.001 0.782 0.007 HK1 0.724 0.0020.718 0.002 HLF 0.580 <.001 0.571 <.001 0.759 0.008 0.750 0.004 HNF1B0.669 <.001 HPS1 0.764 0.008 HSD17B10 0.802 0.045 HSD17B2 0.723 0.048HSD3B2 0.709 0.010 HSP90AB1 0.780 0.034 0.809 0.041 HSPA5 0.738 0.017HSPB1 0.770 0.006 0.801 0.032 HSPB2 0.788 0.035 ICAM1 0.728 0.015 0.7160.010 IER3 0.735 0.016 0.637 <.001 0.802 0.035 IFIT1 0.647 <.001 0.7550.029 IGF1 0.675 <.001 0.603 <.001 0.762 0.006 0.770 0.030 IGF2 0.7610.011 IGFBP2 0.601 <.001 0.605 <.001 IGFBP5 0.702 <.001 IGFBP6 0.628<.001 0.726 0.003 IL1B 0.676 0.002 0.716 0.004 IL6 0.688 0.005 0.7660.044 IL6R 0.786 0.036 IL6ST 0.618 <.001 0.639 <.001 0.785 0.027 0.8130.042 IL8 0.635 <.001 0.628 <.001 ILK 0.734 0.018 0.753 0.026 ING5 0.684<.001 0.681 <.001 0.756 0.006 ITGA4 0.778 0.040 ITGA5 0.762 0.026 ITGA60.811 0.038 ITGA7 0.592 <.001 0.715 0.006 0.710 0.002 ITGAD 0.576 0.006ITGB4 0.693 0.003 ITPR1 0.789 0.029 JUN 0.572 <.001 0.581 <.001 0.7770.019 JUNB 0.732 0.030 0.707 0.016 KCTD12 0.758 0.036 KIT 0.691 0.0090.738 0.028 KLC1 0.741 0.024 0.781 0.024 KLF6 0.733 0.018 0.727 0.014KLK1 0.744 0.028 KLK2 0.697 0.002 0.679 <.001 KLK3 0.725 <.001 0.715<.001 0.841 0.023 KRT15 0.660 <.001 0.577 <.001 0.750 0.002 KRT18 0.623<.001 0.642 <.001 0.702 <.001 0.760 0.006 KRT2 0.740 0.044 KRT5 0.674<.001 0.588 <.001 0.769 0.005 KRT8 0.768 0.034 L1CAM 0.737 0.036 LAG30.711 0.013 0.748 0.029 LAMA4 0.649 0.009 LAMB3 0.709 0.002 0.684 0.0060.768 0.006 LGALS3 0.652 <.001 0.752 0.015 0.805 0.028 LIG3 0.728 0.0160.667 <.001 LRP1 0.811 0.043 MDM2 0.788 0.033 MGMT 0.645 <.001 0.7660.015 MICA 0.796 0.043 0.676 <.001 MPPED2 0.675 <.001 0.616 <.001 0.7500.006 MRC1 0.788 0.028 MTSS1 0.654 <.001 0.793 0.036 MYBPC1 0.706 <.0010.534 <.001 0.773 0.004 0.692 <.001 NCAPD3 0.658 <.001 0.566 <.001 0.7530.011 0.733 0.009 NCOR1 0.838 0.045 NEXN 0.748 0.025 0.785 0.020 NFAT50.531 <.001 0.626 <.001 NFATC2 0.759 0.024 OAZ1 0.766 0.024 OLFML3 0.648<.001 0.748 0.005 0.639 <.001 0.675 <.001 OR51E2 0.823 0.034 PAGE4 0.599<.001 0.698 0.002 0.606 <.001 0.726 <.001 PCA3 0.705 <.001 0.647 <.001PCDHGB7 0.712 <.001 PGF 0.790 0.039 PLG 0.764 0.048 PLP2 0.766 0.037PPAP2B 0.589 <.001 0.647 <.001 0.691 <.001 0.765 0.013 PPP1R12A 0.6730.001 0.677 0.001 0.807 0.045 PRIMA1 0.622 <.001 0.712 0.008 0.740 0.013PRKCA 0.637 <.001 0.694 <.001 PRKCB 0.741 0.020 0.664 <.001 PROM1 0.5990.017 0.527 0.042 0.610 0.006 0.420 0.002 PTCH1 0.752 0.027 0.762 0.011PTEN 0.779 0.011 0.802 0.030 0.788 0.009 PTGS2 0.639 <.001 0.606 <.001PTHLH 0.632 0.007 0.739 0.043 0.654 0.002 0.740 0.015 PTK2B 0.775 0.0190.831 0.028 0.810 0.017 PTPN1 0.721 0.012 0.737 0.024 PYCARD 0.702 0.005RAB27A 0.736 0.008 RAB30 0.761 0.011 RARB 0.746 0.010 RASSF1 0.805 0.043RHOB 0.755 0.029 0.672 0.001 RLN1 0.742 0.036 0.740 0.036 RND3 0.607<.001 0.633 <.001 RNF114 0.782 0.041 0.747 0.013 SDC2 0.714 0.002 SDHC0.698 <.001 0.762 0.029 SERPINA3 0.752 0.030 SERPINB5 0.669 0.014 SH3RF20.705 0.012 0.568 <.001 0.755 0.016 SLC22A3 0.650 <.001 0.582 <.001SMAD4 0.636 <.001 0.684 0.002 0.741 0.007 0.738 0.007 SMARCD1 0.7570.001 SMO 0.790 0.049 0.766 0.013 SOD1 0.741 0.037 0.713 0.007 SORBS10.684 0.003 0.732 0.008 0.788 0.049 SPDEF 0.840 0.012 SPINT1 0.837 0.048SRC 0.674 <.001 0.671 <.001 SRD5A2 0.553 <.001 0.588 <.001 0.618 <.0010.701 <.001 ST5 0.747 0.012 0.761 0.010 0.780 0.016 0.832 0.041 STAT30.735 0.020 STAT5A 0.731 0.005 0.743 0.009 0.817 0.027 STAT5B 0.708<.001 0.696 0.001 SUMO1 0.815 0.037 SVIL 0.689 0.003 0.739 0.008 0.7610.011 TBP 0.792 0.037 TFF3 0.719 0.007 0.664 0.001 TGFB1I1 0.676 0.0030.707 0.007 0.709 0.005 0.777 0.035 TGFB2 0.741 0.010 0.785 0.017 TGFBR20.759 0.022 TIMP3 0.785 0.037 TMPRSS2 0.780 0.012 0.742 <.001 TNF 0.6540.007 0.682 0.006 TNFRSF10B 0.623 <.001 0.681 <.001 0.801 0.018 0.8150.019 TNFSF10 0.721 0.004 TP53 0.759 0.011 TP63 0.737 0.020 0.754 0.007TPM2 0.609 <.001 0.671 <.001 0.673 <.001 0.789 0.031 TRAF3IP2 0.7950.041 0.727 0.005 TRO 0.793 0.033 0.768 0.027 0.814 0.023 TUBB2A 0.626<.001 0.590 <.001 VCL 0.613 <.001 0.701 0.011 VIM 0.716 0.005 0.7920.025 WFDC1 0.824 0.029 YY1 0.668 <.001 0.787 0.014 0.716 0.001 0.8190.011 ZFHX3 0.732 <.001 0.709 <.001 ZFP36 0.656 0.001 0.609 <.001 0.8180.045 ZNF827 0.750 0.022

Tables 6A and 6B provide genes that were significantly associated(p<0.05), positively or negatively, with recurrence (cRFI, bRFI) afteradjusting for Gleason pattern in the primary and/or highest Gleasonpattern. Increased expression of genes in Table 6A is negativelyassociated with good prognosis, while increased expression of gene inTable 6B is positively associated with good prognosis.

TABLE 6A Table 6A. Genes significantly (p < 0.05) associated with cRFIor bRFI after adjustment for Gleason pattern in the primary Gleasonpattern or highest Gleason pattern with a hazard ratio (HR) > 1.0(increased expression is negatively associated with good prognosis) cRFIcRFI bRFI bRFI Official Primary Pattern Highest Pattern Primary PatternHighest Pattern Symbol HR p-value HR p-value HR p-value HR p-valueAKR1C3 1.258 0.039 ANLN 1.292 0.023 1.449 <.001 1.420 0.001 AQP2 1.1780.008 1.287 <.001 ASAP2 1.396 0.015 ASPN 1.809 <.001 1.508 0.009 1.5060.002 1.438 0.002 BAG5 1.367 0.012 BAX 1.234 0.044 BGN 1.465 0.009 1.3420.046 BIRC5 1.338 0.008 1.364 0.004 1.279 0.006 BMP6 1.369 0.015 1.5180.002 BUB1 1.239 0.024 1.227 0.001 1.236 0.004 CACNA1D 1.337 0.025 CADPS1.280 0.029 CCNE2 1.256 0.043 1.577 <.001 1.324 0.001 CD276 1.320 0.0291.396 0.007 1.279 0.033 CDC20 1.298 0.016 1.334 0.002 1.257 0.032 1.2790.003 CDH7 1.258 0.047 1.338 0.013 CDKN2B 1.342 0.032 1.488 0.009 CDKN2C1.344 0.010 1.450 <.001 CDKN3 1.284 0.012 CENPF 1.289 0.048 1.498 0.0011.344 0.010 COL1A1 1.481 0.003 1.506 0.002 COL3A1 1.459 0.004 1.4300.013 COL4A1 1.396 0.015 COL8A1 1.413 0.008 CRISP3 1.346 0.012 1.3100.025 CTHRC1 1.588 0.002 DDIT4 1.363 0.020 1.379 0.028 DICER1 1.2940.008 ENY2 1.269 0.024 FADD 1.307 0.010 FAS 1.243 0.025 FGF5 1.328 0.002GNPTAB 1.246 0.037 GREM1 1.332 0.024 1.377 0.013 1.373 0.011 HDAC1 1.3010.018 1.237 0.021 HSD17B4 1.277 0.011 IFN-γ 1.219 0.048 IMMT 1.230 0.049INHBA 1.866 <.001 1.944 <.001 JAG1 1.298 0.030 KCNN2 1.378 0.020 1.2820.017 KHDRBS3 1.353 0.029 1.305 0.014 LAMA3 1.344 <.001 1.232 0.048LAMC1 1.396 0.015 LIMS1 1.337 0.004 LOX 1.355 0.001 1.341 0.002 LTBP21.304 0.045 MAGEA4 1.215 0.024 MANF 1.460 <.001 MCM6 1.287 0.042 1.2140.046 MELK 1.329 0.002 MMP11 1.281 0.050 MRPL13 1.266 0.021 MYBL2 1.453<.001 1.274 0.019 MYC 1.265 0.037 MYO6 1.278 0.047 NETO2 1.322 0.022NFKB1 1.255 0.032 NOX4 1.266 0.041 OR51E1 1.566 <.001 1.428 0.003 PATE11.242 <.001 1.347 <.001 1.177 0.011 PCNA 1.251 0.025 PEX10 1.302 0.028PGD 1.335 0.045 1.379 0.014 1.274 0.025 PIM1 1.254 0.019 PLA2G7 1.2890.025 1.250 0.031 PLAU 1.267 0.031 PSMD13 1.333 0.005 PTK6 1.432 <.0011.577 <.001 1.223 0.040 PTTG1 1.279 0.013 1.308 0.006 RAGE 1.329 0.011RALA 1.363 0.044 1.471 0.003 RGS7 1.120 0.040 1.173 0.031 RRM1 1.4900.004 1.527 <.001 SESN3 1.353 0.017 SFRP4 1.370 0.025 SHMT2 1.460 0.0081.410 0.006 1.407 0.008 1.345 <.001 SKIL 1.307 0.025 SLC25A21 1.4140.002 1.330 0.004 SMARCC2 1.219 0.049 SPARC 1.431 0.005 TFDP1 1.2830.046 1.345 0.003 THBS2 1.456 0.005 1.431 0.012 TK1 1.214 0.015 1.2220.006 TOP2A 1.367 0.018 1.518 0.001 1.480 <.001 TPX2 1.513 0.001 1.607<.001 1.588 <.001 1.481 <.001 UBE2T 1.409 0.002 1.285 0.018 UGT2B151.216 0.009 1.182 0.021 XIAP 1.336 0.037 1.194 0.043

TABLE 6B Table 6B. Genes significantly (p < 0.05) associated with cRFIor bRFI after adjustment for Gleason pattern in the primary Gleasonpattern or highest Gleason pattern with hazard ration (HR) < 1.0(increased expression is positively associated with good prognosis) cRFIcRFI bRFI bRFI Official Primary Pattern Highest Pattern Primary PatternHighest Pattern Symbol HR p-value HR p-value HR p-value HR p-value AAMP0.660 0.001 0.675 <.001 0.836 0.045 ABCA5 0.807 0.014 0.737 <.001 0.8450.030 ABCC1 0.780 0.038 0.794 0.015 ABCG2 0.807 0.035 ABHD2 0.720 0.002ADH5 0.750 0.034 AKAP1 0.721 <.001 ALDH1A2 0.735 0.009 0.592 <.001 0.7560.007 0.781 0.021 ANGPT2 0.741 0.036 ANPEP 0.637 <.001 0.536 <.001 ANXA20.762 0.044 APOE 0.707 0.013 APRT 0.727 0.004 0.771 0.006 ATXN1 0.7250.013 AURKA 0.784 0.037 0.735 0.003 AXIN2 0.744 0.004 0.630 <.001 AZGP10.672 <.001 0.720 <.001 0.764 0.001 BAD 0.687 <.001 BAK1 0.783 0.014BCL2 0.777 0.033 0.772 0.036 BIK 0.768 0.040 BIN1 0.691 <.001 BTRC 0.7760.029 C7 0.707 0.004 0.791 0.024 CADM1 0.587 <.001 0.593 <.001 CASP10.773 0.023 0.820 0.025 CAV1 0.753 0.014 CAV2 0.627 0.009 0.682 0.003CCL2 0.740 0.019 CCNH 0.736 0.003 CCR1 0.755 0.022 CD1A 0.740 0.025 CD440.590 <.001 0.637 <.001 CD68 0.757 0.026 CD82 0.778 0.012 0.759 0.016CDC25B 0.760 0.021 CDK3 0.762 0.024 0.774 0.007 CDKN1A 0.714 0.015CDKN1C 0.738 0.014 0.768 0.021 COL6A1 0.690 <.001 0.805 0.048 CSF1 0.6750.002 0.779 0.036 CSK 0.825 0.004 CTNNB1 0.884 0.045 0.888 0.027 CTSB0.740 0.017 0.676 0.003 0.755 0.010 CTSD 0.673 0.031 0.722 0.009 CTSK0.804 0.034 CTSL2 0.748 0.019 CXCL12 0.731 0.017 CYP3A5 0.523 <.0010.518 <.001 CYR61 0.744 0.041 DAP 0.755 0.011 DARC 0.763 0.029 DDR20.813 0.041 DES 0.743 0.020 DHRS9 0.606 0.001 DHX9 0.916 0.021 DIAPH10.749 0.036 0.688 0.003 DLGAP1 0.758 0.042 0.676 0.002 DLL4 0.779 0.010DNM3 0.732 0.007 DPP4 0.732 0.004 0.750 0.014 DPT 0.704 0.014 DUSP60.662 <.001 0.665 0.001 EBNA1BP2 0.828 0.019 EDNRA 0.782 0.048 EGF 0.7120.023 EGR1 0.678 0.004 0.725 0.028 EGR3 0.680 0.006 0.738 0.027 EIF2C20.789 0.032 EIF2S3 0.759 0.012 ELK4 0.745 0.024 EPHA2 0.661 0.007 EPHA30.781 0.026 0.828 0.037 ERBB2 0.791 0.022 0.760 0.014 0.789 0.006 ERBB30.757 0.009 ERCC1 0.760 0.008 ESR1 0.742 0.014 ESR2 0.711 0.038 ETV40.714 0.035 FAM107A 0.619 <.001 0.710 0.011 0.781 0.019 FAM13C 0.664<.001 0.686 <.001 0.813 0.014 FAM49B 0.670 <.001 0.793 0.014 0.815 0.0440.843 0.047 FASLG 0.616 0.004 0.813 0.038 FGF10 0.751 0.028 0.766 0.019FGF17 0.718 0.031 0.765 0.019 FGFR2 0.740 0.009 0.738 0.002 FKBP5 0.7490.031 FLNC 0.826 0.029 FLT1 0.779 0.045 0.729 0.006 FLT4 0.815 0.024 FOS0.657 0.003 0.656 0.004 FSD1 0.763 0.017 FYN 0.716 0.004 0.792 0.024GADD45B 0.692 0.009 0.697 0.010 GDF15 0.767 0.016 GHR 0.701 0.002 0.7040.002 0.640 <.001 GNRH1 0.778 0.039 GPM6B 0.749 0.010 0.750 0.010 0.8270.037 GRB7 0.696 0.005 GSK3B 0.726 0.005 GSN 0.660 <.001 0.752 0.019GSTM1 0.710 0.004 0.676 <.001 GSTM2 0.643 <.001 0.767 0.015 HK1 0.7980.035 HLA-G 0.660 0.013 HLF 0.644 <.001 0.727 0.011 HNF1B 0.755 0.013HPS1 0.756 0.006 0.791 0.043 HSD17B10 0.737 0.006 HSD3B2 0.674 0.003HSP90AB1 0.763 0.015 HSPB1 0.787 0.020 0.778 0.015 HSPE1 0.794 0.039ICAM1 0.664 0.003 IER3 0.699 0.003 0.693 0.010 IFIT1 0.621 <.001 0.7330.027 IGF1 0.751 0.017 0.655 <.001 IGFBP2 0.599 <.001 0.605 <.001 IGFBP50.745 0.007 0.775 0.035 IGFBP6 0.671 0.005 IL1B 0.732 0.016 0.717 0.005IL6 0.763 0.040 IL6R 0.764 0.022 IL6ST 0.647 <.001 0.739 0.012 IL8 0.7110.015 0.694 0.006 ING5 0.729 0.007 0.727 0.003 ITGA4 0.755 0.009 ITGA50.743 0.018 0.770 0.034 ITGA6 0.816 0.044 0.772 0.006 ITGA7 0.680 0.004ITGAD 0.590 0.009 ITGB4 0.663 <.001 0.658 <.001 0.759 0.004 JUN 0.6560.004 0.639 0.003 KIAA0196 0.737 0.011 KIT 0.730 0.021 0.724 0.008 KLC10.755 0.035 KLK1 0.706 0.008 KLK2 0.740 0.016 0.723 0.001 KLK3 0.7650.006 0.740 0.002 KRT1 0.774 0.042 KRT15 0.658 <.001 0.632 <.001 0.7640.008 KRT18 0.703 0.004 0.672 <.001 0.779 0.015 0.811 0.032 KRT5 0.686<.001 0.629 <.001 0.802 0.023 KRT8 0.763 0.034 0.771 0.022 L1CAM 0.7480.041 LAG3 0.693 0.008 0.724 0.020 LAMA4 0.689 0.039 LAMB3 0.667 <.0010.645 <.001 0.773 0.006 LGALS3 0.666 <.001 0.822 0.047 LIG3 0.723 0.008LRP1 0.777 0.041 0.769 0.007 MDM2 0.688 <.001 MET 0.709 0.010 0.7360.028 0.715 0.003 MGMT 0.751 0.031 MICA 0.705 0.002 MPPED2 0.690 0.0010.657 <.001 0.708 <.001 MRC1 0.812 0.049 MSH6 0.860 0.049 MTSS1 0.6860.001 MVP 0.798 0.034 0.761 0.033 MYBPC1 0.754 0.009 0.615 <.001 NCAPD30.739 0.021 0.664 0.005 NEXN 0.798 0.037 NFAT5 0.596 <.001 0.732 0.005NFATC2 0.743 0.016 0.792 0.047 NOS3 0.730 0.012 0.757 0.032 OAZ1 0.7320.020 0.705 0.002 OCLN 0.746 0.043 0.784 0.025 OLFML3 0.711 0.002 0.709<.001 0.720 0.001 OMD 0.729 0.011 0.762 0.033 OSM 0.813 0.028 PAGE40.668 0.003 0.725 0.004 0.688 <.001 0.766 0.005 PCA3 0.736 0.001 0.691<.001 PCDHGB7 0.769 0.019 0.789 0.022 PIK3CA 0.768 0.010 PIK3CG 0.7920.019 0.758 0.009 PLG 0.682 0.009 PPAP2B 0.688 0.005 0.815 0.046PPP1R12A 0.731 0.026 0.775 0.042 PRIMA1 0.697 0.004 0.757 0.032 PRKCA0.743 0.019 PRKCB 0.756 0.036 0.767 0.029 PROM1 0.640 0.027 0.699 0.0340.503 0.013 PTCH1 0.730 0.018 PTEN 0.779 0.015 0.789 0.007 PTGS2 0.644<.001 0.703 0.007 PTHLH 0.655 0.012 0.706 0.038 0.634 0.001 0.665 0.003PTK2B 0.779 0.023 0.702 0.002 0.806 0.015 0.806 0.024 PYCARD 0.659 0.001RAB30 0.779 0.033 0.754 0.014 RARB 0.787 0.043 0.742 0.009 RASSF1 0.7540.005 RHOA 0.796 0.041 0.819 0.048 RND3 0.721 0.011 0.743 0.028 SDC10.707 0.011 SDC2 0.745 0.002 SDHC 0.750 0.013 SERPINA3 0.730 0.016SERPINB5 0.715 0.041 SH3RF2 0.698 0.025 SIPA1L1 0.796 0.014 0.820 0.004SLC22A3 0.724 0.014 0.700 0.008 SMAD4 0.668 0.002 0.771 0.016 SMARCD10.726 <.001 0.700 0.001 0.812 0.028 SMO 0.785 0.027 SOD1 0.735 0.012SORBS1 0.785 0.039 SPDEF 0.818 0.002 SPINT1 0.761 0.024 0.773 0.006 SRC0.709 <.001 0.690 <.001 SRD5A1 0.746 0.010 0.767 0.024 0.745 0.003SRD5A2 0.575 <.001 0.669 0.001 0.674 <.001 0.781 0.018 ST5 0.774 0.027STAT1 0.694 0.004 STAT5A 0.719 0.004 0.765 0.006 0.834 0.049 STAT5B0.704 0.001 0.744 0.012 SUMO1 0.777 0.014 SVIL 0.771 0.026 TBP 0.7740.031 TFF3 0.742 0.015 0.719 0.024 TGFB1I1 0.763 0.048 TGFB2 0.729 0.0110.758 0.002 TMPRSS2 0.810 0.034 0.692 <.001 TNF 0.727 0.022 TNFRSF10A0.805 0.025 TNFRSF10B 0.581 <.001 0.738 0.014 0.809 0.034 TNFSF10 0.7510.015 0.700 <.001 TP63 0.723 0.018 0.736 0.003 TPM2 0.708 0.010 0.7340.014 TRAF3IP2 0.718 0.004 TRO 0.742 0.012 TSTA3 0.774 0.028 TUBB2A0.659 <.001 0.650 <.001 TYMP 0.695 0.002 VCL 0.683 0.008 VIM 0.778 0.040WDR19 0.775 0.014 XRCC5 0.793 0.042 YY1 0.751 0.025 0.810 0.008 ZFHX30.760 0.005 0.726 0.001 ZFP36 0.707 0.008 0.672 0.003 ZNF827 0.667 0.0020.792 0.039

Tables 7A and 7B provide genes significantly associated (p<0.05),positively or negatively, with clinical recurrence (cRFI) in negativeTMPRSS fusion specimens in the primary or highest Gleason patternspecimen. Increased expression of genes in Table 7A is negativelyassociated with good prognosis, while increased expression of genes inTable 7B is positively associated with good prognosis.

TABLE 7A Table 7A. Genes significantly (p < 0.05) associated with cRFIfor TMPRSS2-ERG fusion negative in the primary Gleason pattern orhighest Gleason pattern with hazard ratio (HR) > 1.0 (increasedexpression is negatively associated with good prognosis) Primary HighestPattern Pattern Official Symbol HR p-value HR p-value ANLN 1.42 0.0121.36 0.004 AQP2 1.25 0.033 ASPN 2.48 <.001 1.65 <.001 BGN 2.04 <.0011.45 0.007 BIRC5 1.59 <.001 1.37 0.005 BMP6 1.95 <.001 1.43 0.012 BMPR1B1.93 0.002 BUB1 1.51 <.001 1.35 <.001 CCNE2 1.48 0.007 CD276 1.93 <.0011.79 <.001 CDC20 1.49 0.004 1.47 <.001 CDC6 1.52 0.009 1.34 0.022 CDKN2B1.54 0.008 1.55 0.003 CDKN2C 1.55 0.003 1.57 <.001 CDKN3 1.34 0.026CENPF 1.63 0.002 1.33 0.018 CKS2 1.50 0.026 1.43 0.009 CLTC 1.46 0.014COL1A1 1.98 <.001 1.50 0.002 COL3A1 2.03 <.001 1.42 0.007 COL4A1 1.810.002 COL8A1 1.63 0.004 1.60 0.001 CRISP3 1.31 0.016 CTHRC1 1.67 0.0061.48 0.005 DDIT4 1.49 0.037 ENY2 1.29 0.039 EZH2 1.35 0.016 F2R 1.460.034 1.46 0.007 FAP 1.66 0.006 1.38 0.012 FGF5 1.46 0.001 GNPTAB 1.490.013 HSD17B4 1.34 0.039 1.44 0.002 INHBA 2.92 <.001 2.19 <.001 JAG11.38 0.042 KCNN2 1.71 0.002 1.73 <.001 KHDRBS3 1.46 0.015 KLK14 1.280.034 KPNA2 1.63 0.016 LAMC1 1.41 0.044 LOX 1.29 0.036 LTBP2 1.57 0.017MELK 1.38 0.029 MMP11 1.69 0.002 1.42 0.004 MYBL2 1.78 <.001 1.49 <.001NETO2 2.01 <.001 1.43 0.007 NME1 1.38 0.017 PATE1 1.43 <.001 1.24 0.005PEX10 1.46 0.030 PGD 1.77 0.002 POSTN 1.49 0.037 1.34 0.026 PPFIA3 1.510.012 PPP3CA 1.46 0.033 1.34 0.020 PTK6 1.69 <.001 1.56 <.001 PTTG1 1.350.028 RAD51 1.32 0.048 RALBP1 1.29 0.042 RGS7 1.18 0.012 1.32 0.009 RRM11.57 0.016 1.32 0.041 RRM2 1.30 0.039 SAT1 1.61 0.007 SESN3 1.76 <.0011.36 0.020 SFRP4 1.55 0.016 1.48 0.002 SHMT2 2.23 <.001 1.59 <.001 SPARC1.54 0.014 SQLE 1.86 0.003 STMN1 2.14 <.001 THBS2 1.79 <.001 1.43 0.009TK1 1.30 0.026 TOP2A 2.03 <.001 1.47 0.003 TPD52 1.63 0.003 TPX2 2.11<.001 1.63 <.001 TRAP1 1.46 0.023 UBE2C 1.57 <.001 1.58 <.001 UBE2G11.56 0.008 UBE2T 1.75 <.001 UGT2B15 1.31 0.036 1.33 0.004 UHRF1 1.460.007 UTP23 1.52 0.017

TABLE 7B Table 7B. Genes significantly (p < 0.05) associated with cRFIfor TMPRSS2-ERG fusion negative in the primary Gleason pattern orhighest Gleason pattern with hazard ratio (HR) < 1.0 (increasedexpression is positively associated with good prognosis) Primary HighestPattern Pattern Official Symbol HR p-value HR p-value AAMP 0.56 <.0010.65 0.001 ABCA5 0.64 <.001 0.71 <.001 ABCB1 0.62 0.004 ABCC3 0.74 0.031ABCG2 0.78 0.050 ABHD2 0.71 0.035 ACOX2 0.54 <.001 0.71 0.007 ADH5 0.49<.001 0.61 <.001 AKAP1 0.77 0.031 0.76 0.013 AKR1C1 0.65 0.006 0.780.044 AKT1 0.72 0.020 AKT3 0.75 <.001 ALDH1A2 0.53 <.001 0.60 <.001AMPD3 0.62 <.001 0.78 0.028 ANPEP 0.54 <.001 0.61 <.001 ANXA2 0.63 0.0080.74 0.016 ARHGAP29 0.67 0.005 0.77 0.016 ARHGDIB 0.64 0.013 ATP5J 0.570.050 ATXN1 0.61 0.004 0.77 0.043 AXIN2 0.51 <.001 0.62 <.001 AZGP1 0.61<.001 0.64 <.001 BCL2 0.64 0.004 0.75 0.029 BIN1 0.52 <.001 0.74 0.010BTG3 0.75 0.032 0.75 0.010 BTRC 0.69 0.011 C7 0.51 <.001 0.67 <.001CADM1 0.49 <.001 0.76 0.034 CASP1 0.71 0.010 0.74 0.007 CAV1 0.73 0.015CCL5 0.67 0.018 0.67 0.003 CCNH 0.63 <.001 0.75 0.004 CCR1 0.77 0.032CD164 0.52 <.001 0.63 <.001 CD44 0.53 <.001 0.74 0.014 CDH10 0.69 0.040CDH18 0.40 0.011 CDK14 0.75 0.013 CDK2 0.81 0.031 CDK3 0.73 0.022 CDKN1A0.68 0.038 CDKN1C 0.62 0.003 0.72 0.005 COL6A1 0.54 <.001 0.70 0.004COL6A3 0.64 0.004 CSF1 0.56 <.001 0.78 0.047 CSRP1 0.40 <.001 0.66 0.002CTGF 0.66 0.015 0.74 0.027 CTNNB1 0.69 0.043 CTSB 0.60 0.002 0.71 0.011CTSS 0.67 0.013 CXCL12 0.56 <.001 0.77 0.026 CYP3A5 0.43 <.001 0.63<.001 CYR61 0.43 <.001 0.58 <.001 DAG1 0.72 0.012 DARC 0.66 0.016 DDR20.65 0.007 DES 0.52 <.001 0.74 0.018 DHRS9 0.54 0.007 DICER1 0.70 0.044DLC1 0.75 0.021 DLGAP1 0.55 <.001 0.72 0.005 DNM3 0.61 0.001 DPP4 0.55<.001 0.77 0.024 DPT 0.48 <.001 0.61 <.001 DUSP1 0.47 <.001 0.59 <.001DUSP6 0.65 0.009 0.65 0.002 DYNLL1 0.74 0.045 EDNRA 0.61 0.002 0.750.038 EFNB2 0.71 0.043 EGR1 0.43 <.001 0.58 <.001 EGR3 0.47 <.001 0.66<.001 EIF5 0.77 0.028 ELK4 0.49 <.001 0.72 0.012 EPHA2 0.70 0.007 EPHA30.62 <.001 0.72 0.009 EPHB2 0.68 0.009 ERBB2 0.64 <.001 0.63 <.001 ERBB30.69 0.018 ERCC1 0.69 0.019 0.77 0.021 ESR2 0.61 0.020 FAAH 0.57 <.0010.77 0.035 FABP5 0.67 0.035 FAM107A 0.42 <.001 0.59 <.001 FAM13C 0.53<.001 0.59 <.001 FAS 0.71 0.035 FASLG 0.56 0.017 0.67 0.014 FGF10 0.570.002 FGF17 0.70 0.039 0.70 0.010 FGF7 0.63 0.005 0.70 0.004 FGFR2 0.630.003 0.71 0.003 FKBP5 0.72 0.020 FLNA 0.48 <.001 0.74 0.022 FOS 0.45<.001 0.56 <.001 FOXO1 0.59 <.001 FOXQ1 0.57 <.001 0.69 0.008 FYN 0.620.001 0.74 0.013 G6PD 0.77 0.014 GADD45A 0.73 0.045 GADD45B 0.45 <.0010.64 0.001 GDF15 0.58 <.001 GHR 0.62 0.008 0.68 0.002 GPM6B 0.60 <.0010.70 0.003 GSK3B 0.71 0.016 0.71 0.006 GSN 0.46 <.001 0.66 <.001 GSTM10.56 <.001 0.62 <.001 GSTM2 0.47 <.001 0.67 <.001 HGD 0.72 0.002 HIRIP30.69 0.021 0.69 0.002 HK1 0.68 0.005 0.73 0.005 HLA-G 0.54 0.024 0.650.013 HLF 0.41 <.001 0.68 0.001 HNF1B 0.55 <.001 0.59 <.001 HPS1 0.740.015 0.76 0.025 HSD17B3 0.65 0.031 HSPB2 0.62 0.004 0.76 0.027 ICAM10.61 0.010 IER3 0.55 <.001 0.67 0.003 IFIT1 0.57 <.001 0.70 0.008 IFNG0.69 0.040 IGF1 0.63 <.001 0.59 <.001 IGF2 0.67 0.019 0.70 0.005 IGFBP20.53 <.001 0.63 <.001 IGFBP5 0.57 <.001 0.71 0.006 IGFBP6 0.41 <.0010.71 0.012 IL10 0.59 0.020 IL1B 0.53 <.001 0.70 0.005 IL6 0.55 0.001IL6ST 0.45 <.001 0.68 <.001 IL8 0.60 0.005 0.70 0.008 ILK 0.68 0.0290.76 0.036 ING5 0.54 <.001 0.82 0.033 ITGA1 0.66 0.017 ITGA3 0.70 0.020ITGA5 0.64 0.011 ITGA6 0.66 0.003 0.74 0.006 ITGA7 0.50 <.001 0.71 0.010ITGB4 0.63 0.014 0.73 0.010 ITPR1 0.55 <.001 ITPR3 0.76 0.007 JUN 0.37<.001 0.54 <.001 JUNB 0.58 0.002 0.71 0.016 KCTD12 0.68 0.017 KIT 0.490.002 0.76 0.043 KLC1 0.61 0.005 0.77 0.045 KLF6 0.65 0.009 KLK1 0.680.036 KLK10 0.76 0.037 KLK2 0.64 <.001 0.73 0.006 KLK3 0.65 <.001 0.760.021 KLRK1 0.63 0.005 KRT15 0.52 <.001 0.58 <.001 KRT18 0.46 <.001 KRT50.51 <.001 0.58 <.001 KRT8 0.53 <.001 L1CAM 0.65 0.031 LAG3 0.58 0.0020.76 0.033 LAMA4 0.52 0.018 LAMB3 0.60 0.002 0.65 0.003 LGALS3 0.52<.001 0.71 0.002 LIG3 0.65 0.011 LRP1 0.61 0.001 0.75 0.040 MGMT 0.660.003 MICA 0.59 0.001 0.68 0.001 MLXIP 0.70 0.020 MMP2 0.68 0.022 MMP90.67 0.036 MPPED2 0.57 <.001 0.66 <.001 MRC1 0.69 0.028 MTSS1 0.63 0.0050.79 0.037 MVP 0.62 <.001 MYBPC1 0.53 <.001 0.70 0.011 NCAM1 0.70 0.0390.77 0.042 NCAPD3 0.52 <.001 0.59 <.001 NDRG1 0.69 0.008 NEXN 0.62 0.002NFAT5 0.45 <.001 0.59 <.001 NFATC2 0.68 0.035 0.75 0.036 NFKBIA 0.700.030 NRG1 0.59 0.022 0.71 0.018 OAZ1 0.69 0.018 0.62 <.001 OLFML3 0.59<.001 0.72 0.003 OR51E2 0.73 0.013 PAGE4 0.42 <.001 0.62 <.001 PCA3 0.53<.001 PCDHGB7 0.70 0.032 PGF 0.68 0.027 0.71 0.013 PGR 0.76 0.041PIK3C2A 0.80 <.001 PIK3CA 0.61 <.001 0.80 0.036 PIK3CG 0.67 0.001 0.760.018 PLP2 0.65 0.015 0.72 0.010 PPAP2B 0.45 <.001 0.69 0.003 PPP1R12A0.61 0.007 0.73 0.017 PRIMA1 0.51 <.001 0.68 0.004 PRKCA 0.55 <.001 0.740.009 PRKCB 0.55 <.001 PROM1 0.67 0.042 PROS1 0.73 0.036 PTCH1 0.690.024 0.72 0.010 PTEN 0.54 <.001 0.64 <.001 PTGS2 0.48 <.001 0.55 <.001PTH1R 0.57 0.003 0.77 0.050 PTHLH 0.55 0.010 PTK2B 0.56 <.001 0.70 0.001PYCARD 0.73 0.009 RAB27A 0.65 0.009 0.71 0.014 RAB30 0.59 0.003 0.720.010 RAGE 0.76 0.011 RARB 0.59 <.001 0.63 <.001 RASSF1 0.67 0.003 RB10.67 0.006 RFX1 0.71 0.040 0.70 0.003 RHOA 0.71 0.038 0.65 <.001 RHOB0.58 0.001 0.71 0.006 RND3 0.54 <.001 0.69 0.003 RNF114 0.59 0.004 0.680.003 SCUBE2 0.77 0.046 SDHC 0.72 0.028 0.76 0.025 SEC23A 0.75 0.029SEMA3A 0.61 0.004 0.72 0.011 SEPT9 0.66 0.013 0.76 0.036 SERPINB5 0.750.039 SH3RF2 0.44 <.001 0.48 <.001 SHH 0.74 0.049 SLC22A3 0.42 <.0010.61 <.001 SMAD4 0.45 <.001 0.66 <.001 SMARCD1 0.69 0.016 SOD1 0.680.042 SORBS1 0.51 <.001 0.73 0.012 SPARCL1 0.58 <.001 0.77 0.040 SPDEF0.77 <.001 SPINT1 0.65 0.004 0.79 0.038 SRC 0.61 <.001 0.69 0.001 SRD5A20.39 <.001 0.55 <.001 ST5 0.61 <.001 0.73 0.012 STAT1 0.64 0.006 STAT30.63 0.010 STAT5A 0.62 0.001 0.70 0.003 STAT5B 0.58 <.001 0.73 0.009SUMO1 0.66 <.001 SVIL 0.57 0.001 0.74 0.022 TBP 0.65 0.002 TFF1 0.650.021 TFF3 0.58 <.001 TGFB1I1 0.51 <.001 0.75 0.026 TGFB2 0.48 <.0010.62 <.001 TGFBR2 0.61 0.003 TIAM1 0.68 0.019 TIMP2 0.69 0.020 TIMP30.58 0.002 TNFRSF10A 0.73 0.047 TNFRSF10B 0.47 <.001 0.70 0.003 TNFSF100.56 0.001 TP63 0.67 0.001 TPM1 0.58 0.004 0.73 0.017 TPM2 0.46 <.0010.70 0.005 TRA2A 0.68 0.013 TRAF3IP2 0.73 0.041 0.71 0.004 TRO 0.720.016 0.71 0.004 TUBB2A 0.53 <.001 0.73 0.021 TYMP 0.70 0.011 VCAM1 0.690.041 VCL 0.46 <.001 VEGFA 0.77 0.039 VEGFB 0.71 0.035 VIM 0.60 0.001XRCC5 0.75 0.026 YY1 0.62 0.008 0.77 0.039 ZFHX3 0.53 <.001 0.58 <.001ZFP36 0.43 <.001 0.54 <.001 ZNF827 0.55 0.001

Tables 8A and 8B provide genes that were significantly associated(p<0.05), positively or negatively, with clinical recurrence (cRFI) inpositive TMPRSS fusion specimens in the primary or highest Gleasonpattern specimen. Increased expression of genes in Table 8A isnegatively associated with good prognosis, while increased expression ofgenes in Table 8B is positively associated with good prognosis.

TABLE 8A Table 8A. Genes significantly (p < 0.05) associated with cRFIfor TMPRSS2-ERG fusion positive in the primary Gleason pattern orhighest Gleason pattern with hazard ratio (HR) > 1.0 (increasedexpression is negatively associated with good prognosis) Primary HighestPattern Pattern Official Symbol HR p-value HR p-value ACTR2 1.78 0.017AKR1C3 1.44 0.013 ALCAM 1.44 0.022 ANLN 1.37 0.046 1.81 <.001 APOE 1.490.023 1.66 0.005 AQP2 1.30 0.013 ARHGDIB 1.55 0.021 ASPN 2.13 <.001 2.43<.001 ATP5E 1.69 0.013 1.58 0.014 BGN 1.92 <.001 2.55 <.001 BIRC5 1.480.006 1.89 <.001 BMP6 1.51 0.010 1.96 <.001 BRCA2 1.41 0.007 BUB1 1.360.007 1.52 <.001 CCNE2 1.55 0.004 1.59 <.001 CD276 1.65 <.001 CDC20 1.68<.001 1.74 <.001 CDH11 1.50 0.017 CDH18 1.36 <.001 CDH7 1.54 0.009 1.460.026 CDKN2B 1.68 0.008 1.93 0.001 CDKN2C 2.01 <.001 1.77 <.001 CDKN31.51 0.002 1.33 0.049 CENPF 1.51 0.007 2.04 <.001 CKS2 1.43 0.034 1.560.007 COL1A1 2.23 <.001 3.04 <.001 COL1A2 1.79 0.001 2.22 <.001 COL3A11.96 <.001 2.81 <.001 COL4A1 1.52 0.020 COL5A1 1.50 0.020 COL5A2 1.640.017 1.55 0.010 COL8A1 1.96 <.001 2.38 <.001 CRISP3 1.68 0.002 1.670.002 CTHRC1 2.06 <.001 CTNND2 1.42 0.046 1.50 0.025 CTSK 1.43 0.049CXCR4 1.82 0.001 1.64 0.007 DDIT4 1.54 0.016 1.58 0.009 DLL4 1.51 0.007DYNLL1 1.50 0.021 1.22 0.002 F2R 2.27 <.001 2.02 <.001 FAP 2.12 <.001FCGR3A 1.94 0.002 FGF5 1.23 0.047 FOXP3 1.52 0.006 1.48 0.018 GNPTAB1.44 0.042 GPR68 1.51 0.011 GREM1 1.91 <.001 2.38 <.001 HDAC1 1.43 0.048HDAC9 1.65 <.001 1.67 0.004 HRAS 1.65 0.005 1.58 0.021 IGFBP3 1.94 <.0011.85 <.001 INHBA 2.03 <.001 2.64 <.001 JAG1 1.41 0.027 1.50 0.008 KCTD121.51 0.017 KHDRBS3 1.48 0.029 1.54 0.014 KPNA2 1.46 0.050 LAMA3 1.350.040 LAMC1 1.77 0.012 LTBP2 1.82 <.001 LUM 1.51 0.021 1.53 0.009 MELK1.38 0.020 1.49 0.001 MKI67 1.37 0.014 MMP11 1.73 <.001 1.69 <.001MRPL13 1.30 0.046 MYBL2 1.56 <.001 1.72 <.001 MYLK3 1.17 0.007 NOX4 1.580.005 1.96 <.001 NRIP3 1.30 0.040 NRP1 1.53 0.021 OLFML2B 1.54 0.024 OSM1.43 0.018 PATE1 1.20 <.001 1.33 <.001 PCNA 1.64 0.003 PEX10 1.41 0.0411.64 0.003 PIK3CA 1.38 0.037 PLK1 1.52 0.009 1.67 0.002 PLOD2 1.65 0.002POSTN 1.79 <.001 2.06 <.001 PTK6 1.67 0.002 2.38 <.001 PTTG1 1.56 0.0021.54 0.003 RAD21 1.61 0.036 1.53 0.005 RAD51 1.33 0.009 RALA 1.95 0.0041.60 0.007 REG4 1.43 0.042 ROBO2 1.46 0.024 RRM1 1.44 0.033 RRM2 1.500.003 1.48 <.001 SAT1 1.42 0.009 1.43 0.012 SEC14L1 1.64 0.002 SFRP42.07 <.001 2.40 <.001 SHMT2 1.52 0.030 1.60 0.001 SLC44A1 1.42 0.039SPARC 1.93 <.001 2.21 <.001 SULF1 1.63 0.006 2.04 <.001 THBS2 1.95 <.0012.26 <.001 THY1 1.69 0.016 1.95 0.002 TK1 1.43 0.003 TOP2A 1.57 0.0022.11 <.001 TPX2 1.84 <.001 2.27 <.001 UBE2C 1.41 0.011 1.44 0.006 UBE2T1.63 0.001 UHRF1 1.51 0.007 1.69 <.001 WISP1 1.47 0.045 WNT5A 1.35 0.0271.63 0.001 ZWINT 1.36 0.045

TABLE 8B Table 8B. Genes significantly (p < 0.05) associated with cRFIfor TMPRSS2-ERG fusion positive in the primary Gleason pattern orhighest Gleason pattern with hazard ratio (HR) < 1.0 (increasedexpression is positively associated with good prognosis) Primary HighestPattern Pattern Official Symbol HR p-value HR p-value AAMP 0.57 0.0070.58 <.001 ABCA5 0.80 0.044 ACE 0.65 0.023 0.55 <.001 ACOX2 0.55 <.001ADH5 0.68 0.022 AKAP1 0.81 0.043 ALDH1A2 0.72 0.036 0.43 <.001 ANPEP0.66 0.022 0.46 <.001 APRT 0.73 0.040 AXIN2 0.60 <.001 AZGP1 0.57 <.0010.65 <.001 BCL2 0.69 0.035 BIK 0.71 0.045 BIN1 0.71 0.004 0.71 0.009BTRC 0.66 0.003 0.58 <.001 C7 0.64 0.006 CADM1 0.61 <.001 0.47 <.001CCL2 0.73 0.042 CCNH 0.69 0.022 CD44 0.56 <.001 0.58 <.001 CD82 0.720.033 CDC25B 0.74 0.028 CDH1 0.75 0.030 0.72 0.010 CDH19 0.56 0.015 CDK30.78 0.045 CDKN1C 0.74 0.045 0.70 0.014 CSF1 0.72 0.037 CTSB 0.69 0.048CTSL2 0.58 0.005 CYP3A5 0.51 <.001 0.30 <.001 DHX9 0.89 0.006 0.87 0.012DLC1 0.64 0.023 DLGAP1 0.69 0.010 0.49 <.001 DPP4 0.64 <.001 0.56 <.001DPT 0.63 0.003 EGR1 0.69 0.035 EGR3 0.68 0.025 EIF2S3 0.70 0.021 EIF50.71 0.030 ELK4 0.71 0.041 0.60 0.003 EPHA2 0.72 0.036 0.66 0.011 EPHB40.65 0.007 ERCC1 0.68 0.023 ESR2 0.64 0.027 FAM107A 0.64 0.003 0.610.003 FAM13C 0.68 0.006 0.55 <.001 FGFR2 0.73 0.033 0.59 <.001 FKBP50.60 0.006 FLNC 0.68 0.024 0.65 0.012 FLT1 0.71 0.027 FOS 0.62 0.006FOXO1 0.75 0.010 GADD45B 0.68 0.020 GHR 0.62 0.006 GPM6B 0.57 <.001GSTM1 0.68 0.015 0.58 <.001 GSTM2 0.65 0.005 0.47 <.001 HGD 0.63 0.0010.71 0.020 HK1 0.67 0.003 0.62 0.002 HLF 0.59 <.001 HNF1B 0.66 0.0040.61 0.001 IER3 0.70 0.026 IGF1 0.63 0.005 0.55 <.001 IGF1R 0.76 0.049IGFBP2 0.59 0.007 0.64 0.003 IL6ST 0.65 0.005 IL8 0.61 0.005 0.66 0.019ILK 0.64 0.015 ING5 0.73 0.033 0.70 0.009 ITGA7 0.72 0.045 0.69 0.019ITGB4 0.63 0.002 KLC1 0.74 0.045 KLK1 0.56 0.002 0.49 <.001 KLK10 0.680.013 KLK11 0.66 0.003 KLK2 0.66 0.045 0.65 0.011 KLK3 0.75 0.048 0.770.014 KRT15 0.71 0.017 0.50 <.001 KRT5 0.73 0.031 0.54 <.001 LAMA5 0.700.044 LAMB3 0.70 0.005 0.58 <.001 LGALS3 0.69 0.025 LIG3 0.68 0.022 MDK0.69 0.035 MGMT 0.59 0.017 0.60 <.001 MGST1 0.73 0.042 MICA 0.70 0.009MPPED2 0.72 0.031 0.54 <.001 MTSS1 0.62 0.003 MYBPC1 0.50 <.001 NCAPD30.62 0.007 0.38 <.001 NCOR1 0.82 0.048 NFAT5 0.60 0.001 0.62 <.001 NRG10.66 0.040 0.61 0.029 NUP62 0.75 0.037 OMD 0.54 <.001 PAGE4 0.64 0.005PCA3 0.66 0.012 PCDHGB7 0.68 0.018 PGR 0.60 0.012 PPAP2B 0.62 0.010PPP1R12A 0.73 0.031 0.58 0.003 PRIMA1 0.65 0.013 PROM1 0.41 0.013 PTCH10.64 0.006 PTEN 0.75 0.047 PTGS2 0.67 0.011 PTK2B 0.66 0.005 PTPN1 0.710.026 RAGE 0.70 0.012 RARB 0.68 0.016 RGS10 0.84 0.034 RHOB 0.66 0.016RND3 0.63 0.004 SDHC 0.73 0.044 0.69 0.016 SERPINA3 0.67 0.011 0.51<.001 SERPINB5 0.42 <.001 SH3RF2 0.66 0.012 0.51 <.001 SLC22A3 0.590.003 0.48 <.001 SMAD4 0.64 0.004 0.49 <.001 SMARCC2 0.73 0.042 SMARCD10.73 <.001 0.76 0.035 SMO 0.64 0.006 SNAI1 0.53 0.008 SOD1 0.60 0.003SRC 0.64 <.001 0.61 <.001 SRD5A2 0.63 0.004 0.59 <.001 STAT3 0.64 0.014STAT5A 0.70 0.032 STAT5B 0.74 0.034 0.63 0.003 SVIL 0.71 0.028 TGFB1I10.68 0.036 TMPRSS2 0.72 0.015 0.67 <.001 TNFRSF10A 0.69 0.010 TNFRSF10B0.67 0.007 0.64 0.001 TNFRSF18 0.38 0.003 TNFSF10 0.71 0.025 TP53 0.680.004 0.57 <.001 TP63 0.75 0.049 0.52 <.001 TPM2 0.62 0.007 TRAF3IP20.71 0.017 0.68 0.005 TRO 0.72 0.033 TUBB2A 0.69 0.038 VCL 0.62 <.001VEGFA 0.71 0.037 WWOX 0.65 0.004 ZFHX3 0.77 0.011 0.73 0.012 ZFP36 0.690.018 ZNF827 0.68 0.013 0.49 <.001

Tables 9A and 9B provide genes significantly associated (p<0.05),positively or negatively, with TMPRSS fusion status in the primaryGleason pattern. Increased expression of genes in Table 9A arepositively associated with TMPRSS fusion positivity, while increasedexpression of genes in Table 10A are negatively associated with TMPRSSfusion positivity.

TABLE 9A Table 9A. Genes significantly (p < 0.05) associated with TMPRSSfusion status in the primary Gleason pattern with odds ratio (OR) > 1.0(increased expression is positively associated with TMPRSS fusionpositivity Official Symbol p-value Odds Ratio ABCC8 <.001 1.86 ALDH18A10.005 1.49 ALKBH3 0.043 1.30 ALOX5 <.001 1.66 AMPD3 <.001 3.92 APEX1<.001 2.00 ARHGDIB <.001 1.87 ASAP2 0.019 1.48 ATXN1 0.013 1.41 BMPR1B<.001 2.37 CACNA1D <.001 9.01 CADPS 0.015 1.39 CD276 0.003 2.25 CDH10.016 1.37 CDH7 <.001 2.22 CDK7 0.025 1.43 COL9A2 <.001 2.58 CRISP3<.001 2.60 CTNND1 0.033 1.48 ECE1 <.001 2.22 EIF5 0.023 1.34 EPHB4 0.0051.51 ERG <.001 14.5 FAM171B 0.047 1.32 FAM73A 0.008 1.45 FASN 0.004 1.50GNPTAB <.001 1.60 GPS1 0.006 1.45 GRB7 0.023 1.38 HDAC1 <.001 4.95 HGD<.001 1.64 HIP1 <.001 1.90 HNF1B <.001 3.55 HSPA8 0.041 1.32 IGF1R 0.0011.73 ILF3 <.001 1.91 IMMT 0.025 1.36 ITPR1 <.001 2.72 ITPR3 <.001 5.91JAG1 0.007 1.42 KCNN2 <.001 2.80 KHDRBS3 <.001 2.63 KIAA0247 0.019 1.38KLK11 <.001 1.98 LAMC1 0.008 1.56 LAMC2 <.001 3.30 LOX 0.009 1.41 LRP10.044 1.30 MAP3K5 <.001 2.06 MAP7 <.001 2.74 MSH2 0.005 1.59 MSH3 0.0061.45 MUC1 0.012 1.42 MYO6 <.001 3.79 NCOR2 0.001 1.62 NDRG1 <.001 6.77NETO2 <.001 2.63 ODC1 <.001 1.98 OR51E1 <.001 2.24 PDE9A <.001 2.21PEX10 <.001 3.41 PGK1 0.022 1.33 PLA2G7 <.001 5.51 PPP3CA 0.047 1.38PSCA 0.013 1.43 PSMD13 0.004 1.51 PTCH1 0.022 1.38 PTK2 0.014 1.38 PTK6<.001 2.29 PTK7 <.001 2.45 PTPRK <.001 1.80 RAB30 0.001 1.60 REG4 0.0181.58 RELA 0.001 1.62 RFX1 0.020 1.43 RGS10 <.001 1.71 SCUBE2 0.009 1.48SEPT9 <.001 3.91 SH3RF2 0.004 1.48 SH3YL1 <.001 1.87 SHH <.001 2.45 SIM2<.001 1.74 SIPA1L1 0.021 1.35 SLC22A3 <.001 1.63 SLC44A1 <.001 1.65SPINT1 0.017 1.39 TFDP1 0.005 1.75 TMPRSS2ERGA 0.002 14E5 TMPRSS2ERGB<.001 1.97 TRIM14 <.001 1.65 TSTA3 0.018 1.38 UAP1 0.046 1.39 UBE2G10.001 1.66 UGDH <.001 2.22 XRCC5 <.001 1.66 ZMYND8 <.001 2.19

TABLE 9B Table 9B. Genes significantly (p < 0.05) associated with TMPRSSfusion status in the primary Gleason pattern with odds ratio (OR) < 1.0(increased expression is negatively associated with TMPRSS fusionpositivity) Official Symbol p-value Odds Ratio ABCC4 0.045 0.77 ABHD2<.001 0.38 ACTR2 0.027 0.73 ADAMTS1 0.024 0.58 ADH5 <.001 0.58 AGTR20.016 0.64 AKAP1 0.013 0.70 AKT2 0.015 0.71 ALCAM <.001 0.45 ALDH1A20.004 0.70 ANPEP <.001 0.43 ANXA2 0.010 0.71 APC 0.036 0.73 APOC1 0.0020.56 APOE <.001 0.44 ARF1 0.041 0.77 ATM 0.036 0.74 AURKB <.001 0.62AZGP1 <.001 0.54 BBC3 0.030 0.74 BCL2 0.012 0.70 BIN1 0.021 0.74 BTG10.004 0.67 BTG3 0.003 0.63 C7 0.023 0.74 CADM1 0.007 0.69 CASP1 0.0110.70 CAV1 0.011 0.71 CCND1 0.019 0.72 CCR1 0.022 0.73 CD44 <.001 0.57CD68 <.001 0.54 CD82 0.002 0.66 CDH5 0.007 0.66 CDKN1A <.001 0.60 CDKN2B<.001 0.54 CDKN2C 0.012 0.72 CDKN3 0.037 0.77 CHN1 0.038 0.75 CKS2 <.0010.48 COL11A1 0.017 0.72 COL1A1 <.001 0.59 COL1A2 0.001 0.62 COL3A1 0.0270.73 COL4A1 0.043 0.76 COL5A1 0.039 0.74 COL5A2 0.026 0.73 COL6A1 0.0080.66 COL6A3 <.001 0.59 COL8A1 0.022 0.74 CSF1 0.011 0.70 CTNNB1 0.0210.69 CTSB <.001 0.62 CTSD 0.036 0.68 CTSK 0.007 0.70 CTSS 0.002 0.64CXCL12 <.001 0.48 CXCR4 0.005 0.68 CXCR7 0.046 0.76 CYR61 0.004 0.65 DAP0.002 0.64 DARC 0.021 0.73 DDR2 0.021 0.73 DHRS9 <.001 0.52 DIAPH1 <.0010.56 DICER1 0.029 0.75 DLC1 0.013 0.72 DLGAP1 <.001 0.60 DLL4 <.001 0.57DPT 0.006 0.68 DUSP1 0.012 0.68 DUSP6 0.001 0.62 DVL1 0.037 0.75 EFNB2<.001 0.32 EGR1 0.003 0.65 ELK4 <.001 0.60 ERBB2 <.001 0.61 ERBB3 0.0450.76 ESR2 0.010 0.70 ETV1 0.042 0.74 FABP5 <.001 0.21 FAM13C 0.006 0.67FCGR3A 0.018 0.72 FGF17 0.009 0.71 FGF6 0.011 0.70 FGF7 0.003 0.63 FN10.006 0.69 FOS 0.035 0.74 FOXP3 0.010 0.71 GABRG2 0.029 0.74 GADD45B0.003 0.63 GDF15 <.001 0.54 GPM6B 0.004 0.67 GPNMB 0.001 0.62 GSN 0.0090.69 HLA-G 0.050 0.74 HLF 0.018 0.74 HPS1 <.001 0.48 HSD17B3 0.003 0.60HSD17B4 <.001 0.56 HSPB1 <.001 0.38 HSPB2 0.002 0.62 IFI30 0.049 0.75IFNG 0.006 0.64 IGF1 0.016 0.73 IGF2 0.001 0.57 IGFBP2 <.001 0.51 IGFBP3<.001 0.59 IGFBP6 <.001 0.57 IL10 <.001 0.62 IL17A 0.012 0.63 IL1A 0.0110.59 IL2 0.001 0.63 IL6ST <.001 0.52 INSL4 0.014 0.71 ITGA1 0.009 0.69ITGA4 0.007 0.68 JUN <.001 0.59 KIT <.001 0.64 KRT76 0.016 0.70 LAG30.002 0.63 LAPTM5 <.001 0.58 LGALS3 <.001 0.53 LTBP2 0.011 0.71 LUM0.012 0.70 MAOA 0.020 0.73 MAP4K4 0.007 0.68 MGST1 <.001 0.54 MMP2 <.0010.61 MPPED2 <.001 0.45 MRC1 0.005 0.67 MTPN 0.002 0.56 MTSS1 <.001 0.53MVP 0.009 0.72 MYBPC1 <.001 0.51 MYLK3 0.001 0.58 NCAM1 <.001 0.59NCAPD3 <.001 0.40 NCOR1 0.004 0.69 NFKBIA <.001 0.63 NNMT 0.006 0.66NPBWR1 0.027 0.67 OAZ1 0.049 0.64 OLFML3 <.001 0.56 OSM <.001 0.64 PAGE10.012 0.52 PDGFRB 0.016 0.73 PECAM1 <.001 0.55 PGR 0.048 0.77 PIK3CA<.001 0.55 PIK3CG 0.008 0.71 PLAU 0.044 0.76 PLK1 0.006 0.68 PLOD2 0.0130.71 PLP2 0.024 0.73 PNLIPRP2 0.009 0.70 PPAP2B <.001 0.62 PRKAR2B <.0010.61 PRKCB 0.044 0.76 PROS1 0.005 0.67 PTEN <.001 0.47 PTGER3 0.007 0.69PTH1R 0.011 0.70 PTK2B <.001 0.61 PTPN1 0.028 0.73 RAB27A <.001 0.21RAD51 <.001 0.51 RAD9A 0.030 0.75 RARB <.001 0.62 RASSF1 0.038 0.76 RECK0.009 0.62 RHOB 0.004 0.64 RHOC <.001 0.56 RLN1 <.001 0.30 RND3 0.0140.72 S100P 0.002 0.66 SDC2 <.001 0.61 SEMA3A 0.001 0.64 SMAD4 <.001 0.64SPARC <.001 0.59 SPARCL1 <.001 0.56 SPINK1 <.001 0.26 SRD5A1 0.039 0.76STAT1 0.026 0.74 STS 0.006 0.64 SULF1 <.001 0.53 TFF3 <.001 0.19 TGFA0.002 0.65 TGFB1I1 0.040 0.77 TGFB2 0.003 0.66 TGFB3 <.001 0.54 TGFBR2<.001 0.61 THY1 <.001 0.63 TIMP2 0.004 0.66 TIMP3 <.001 0.60 TMPRSS2<.001 0.40 TNFSF11 0.026 0.63 TPD52 0.002 0.64 TRAM1 <.001 0.45 TRPC60.002 0.64 TUBB2A <.001 0.49 VCL <.001 0.57 VEGFB 0.033 0.73 VEGFC <.0010.61 VIM 0.012 0.69 WISP1 0.030 0.75 WNT5A <.001 0.50

A molecular field effect was investigated, and determined that theexpression levels of histologically normal-appearing cells adjacent tothe tumor exhibited a molecular signature of prostate cancer. Tables 10Aand 10B provide genes significantly associated (p<0.05), positively ornegatively, with cRFI or bRFI in non-tumor samples. Table 10A isnegatively associated with good prognosis, while increased expression ofgenes in Table 10B is positively associated with good prognosis.

TABLE 10A Table 10A Genes significantly (p < 0.05) associated with cRFIor bRFI in Non-Tumor Samples with hazard ratio (HR) > 1.0 (increasedexpression is negatively associated with good prognosis) cRFI bRFIOfficial Symbol HR p-value HR p-value ALCAM 1.278 0.036 ASPN 1.309 0.032BAG5 1.458 0.004 BRCA2 1.385 <.001 CACNA1D 1.329 0.035 CD164 1.339 0.020CDKN2B 1.398 0.014 COL3A1 1.300 0.035 COL4A1 1.358 0.019 CTNND2 1.3700.001 DARC 1.451 0.003 DICER1 1.345 <.001 DPP4 1.358 0.008 EFNB2 1.3230.007 FASN 1.327 0.035 GHR 1.332 0.048 HSPA5 1.260 0.048 INHBA 1.558<.001 KCNN2 1.264 0.045 KRT76 1.115 <.001 LAMC1 1.390 0.014 LAMC2 1.2160.042 LIG3 1.313 0.030 MAOA 1.405 0.013 MCM6 1.307 0.036 MKI67 1.2710.008 NEK2 1.312 0.016 NPBWR1 1.278 0.035 ODC1 1.320 0.010 PEX10 1.3610.014 PGK1 1.488 0.004 PLA2G7 1.337 0.025 POSTN 1.306 0.043 PTK6 1.3440.005 REG4 1.348 0.009 RGS7 1.144 0.047 SFRP4 1.394 0.009 TARP 1.4120.011 TFF1 1.346 0.010 TGFBR2 1.310 0.035 THY1 1.300 0.038 TMPRSS2ERGA1.333 <.001 TPD52 1.374 0.015 TRPC6 1.272 0.046 UBE2C 1.323 0.007 UHRF11.325 0.021

TABLE 10B Table 10B Genes significantly (p < 0.05) associated with cRFIor bRFI in Non-Tumor Samples with hazard ratio (HR) < 1.0 (increasedexpression is positively associated with good prognosis) cRFI bRFIOfficial Symbol HR p-value HR p-value ABCA5 0.807 0.028 ABCC3 0.7600.019 0.750 0.003 ABHD2 0.781 0.028 ADAM15 0.718 0.005 AKAP1 0.740 0.009AMPD3 0.793 0.013 ANGPT2 0.752 0.027 ANXA2 0.776 0.035 APC 0.755 0.014APRT 0.762 0.025 AR 0.752 0.015 ARHGDIB 0.753 <.001 BIN1 0.738 0.016CADM1 0.711 0.004 CCNH 0.820 0.041 CCR1 0.749 0.007 CDK14 0.772 0.014CDK3 0.819 0.044 CDKN1C 0.808 0.038 CHAF1A 0.634 0.002 0.779 0.045 CHN10.803 0.034 CHRAC1 0.751 0.014 0.779 0.021 COL5A1 0.736 0.012 COL5A20.762 0.013 COL6A1 0.757 0.032 COL6A3 0.757 0.019 CSK 0.663 <.001 0.698<.001 CTSK 0.782 0.029 CXCL12 0.771 0.037 CXCR7 0.753 0.008 CYP3A5 0.7900.035 DDIT4 0.725 0.017 DIAPH1 0.771 0.015 DLC1 0.744 0.004 0.807 0.015DLGAP1 0.708 0.004 DUSP1 0.740 0.034 EDN1 0.742 0.010 EGR1 0.731 0.028EIF3H 0.761 0.024 EIF4E 0.786 0.041 ERBB2 0.664 0.001 ERBB4 0.764 0.036ERCC1 0.804 0.041 ESR2 0.757 0.025 EZH2 0.798 0.048 FAAH 0.798 0.042FAM13C 0.764 0.012 FAM171B 0.755 0.005 FAM49B 0.811 0.043 FAM73A 0.7780.015 FASLG 0.757 0.041 FGFR2 0.735 0.016 FOS 0.690 0.008 FYN 0.7880.035 0.777 0.011 GPNMB 0.762 0.011 GSK3B 0.792 0.038 HGD 0.774 0.017HIRIP3 0.802 0.033 HSP90AB1 0.753 0.013 HSPB1 0.764 0.021 HSPE1 0.6680.001 IFI30 0.732 0.002 IGF2 0.747 0.006 IGFBP5 0.691 0.006 IL6ST 0.7480.010 IL8 0.785 0.028 IMMT 0.708 <.001 ITGA6 0.747 0.008 ITGAV 0.7920.016 ITGB3 0.814 0.034 ITPR3 0.769 0.009 JUN 0.655 0.005 KHDRBS3 0.7640.012 KLF6 0.714 <.001 KLK2 0.813 0.048 LAMA4 0.702 0.009 LAMA5 0.7440.011 LAPTM5 0.740 0.009 LGALS3 0.773 0.036 0.788 0.024 LIMS1 0.8070.012 MAP3K5 0.815 0.034 MAP3K7 0.809 0.032 MAP4K4 0.735 0.018 0.7610.010 MAPKAPK3 0.754 0.014 MICA 0.785 0.019 MTA1 0.808 0.043 MVP 0.6910.001 MYLK3 0.730 0.039 MYO6 0.780 0.037 NCOA1 0.787 0.040 NCOR1 0.8760.020 NDRG1 0.761 <.001 NFAT5 0.770 0.032 NFKBIA 0.799 0.018 NME2 0.7530.005 NUP62 0.842 0.032 OAZ1 0.803 0.043 OLFML2B 0.745 0.023 OLFML30.743 0.009 OSM 0.726 0.018 PCA3 0.714 0.019 PECAM1 0.774 0.023 PIK3C2A0.768 0.001 PIM1 0.725 0.011 PLOD2 0.713 0.008 PPP3CA 0.768 0.040 PROM10.482 <.001 PTEN 0.807 0.012 PTGS2 0.726 0.011 PTTG1 0.729 0.006 PYCARD0.783 0.012 RAB30 0.730 0.002 RAGE 0.792 0.012 RFX1 0.789 0.016 0.7920.010 RGS10 0.781 0.017 RUNX1 0.747 0.007 SDHC 0.827 0.036 SEC23A 0.7520.010 SEPT9 0.889 0.006 SERPINA3 0.738 0.013 SLC25A21 0.788 0.045SMARCD1 0.788 0.010 0.733 0.007 SMO 0.813 0.035 SRC 0.758 0.026 SRD5A20.738 0.005 ST5 0.767 0.022 STAT5A 0.784 0.039 TGFB2 0.771 0.027 TGFB30.752 0.036 THBS2 0.751 0.015 TNFRSF10B 0.739 0.010 TPX2 0.754 0.023TRAF3IP2 0.774 0.015 TRAM1 0.868 <.001 0.880 <.001 TRIM14 0.785 0.047TUBB2A 0.705 0.010 TYMP 0.778 0.024 UAP1 0.721 0.013 UTP23 0.763 0.0070.826 0.018 VCL 0.837 0.040 VEGFA 0.755 0.009 WDR19 0.724 0.005 YBX10.786 0.027 ZFP36 0.744 0.032 ZNF827 0.770 0.043

Table 11 provides genes that are significantly associated (p<0.05) withcRFI or bRFI after adjustment for Gleason pattern or highest Gleasonpattern.

TABLE 11 Table 11 Genes significantly (p < 0.05) associated with cRFI orbRFI after adjustment for Gleason pattern in the primary Gleason patternor highest Gleason pattern Some HR <= 1.0 and some HR > 1.0 cRFI bRFIbRFI Highest Pattern Primary Pattern Highest Pattern Official Symbol HRp-value HR p-value HR p-value HSPA5 0.710 0.009 1.288 0.030 ODC1 0.7410.026 1.343 0.004 1.261 0.046

Tables 12A and 12B provide genes that are significantly associated(p<0.05) with prostate cancer specific survival (PCSS) in the primaryGleason pattern. Increased expression of genes in Table 12A isnegatively associated with good prognosis, while increased expression ofgenes in Table 12B is positively associated with good prognosis.

TABLE 12A Table 12A Genes significantly (p < 0.05) associated withprostate cancer specific survival (PCSS) in the Primary Gleason PatternHR > 1.0 (Increased expression is negatively associated with goodprognosis) Official Symbol HR p-value AKR1C3 1.476 0.016 ANLN 1.5170.006 APOC1 1.285 0.016 APOE 1.490 0.024 ASPN 3.055 <.001 ATP5E 1.7880.012 AURKB 1.439 0.008 BGN 2.640 <.001 BIRC5 1.611 <.001 BMP6 1.4900.021 BRCA1 1.418 0.036 CCNB1 1.497 0.021 CD276 1.668 0.005 CDC20 1.730<.001 CDH11 1.565 0.017 CDH7 1.553 0.007 CDKN2B 1.751 0.003 CDKN2C 1.9930.013 CDKN3 1.404 0.008 CENPF 2.031 <.001 CHAF1A 1.376 0.011 CKS2 1.4990.031 COL1A1 2.574 <.001 COL1A2 1.607 0.011 COL3A1 2.382 <.001 COL4A11.970 <.001 COL5A2 1.938 0.002 COL8A1 2.245 <.001 CTHRC1 2.085 <.001CXCR4 1.783 0.007 DDIT4 1.535 0.030 DYNLL1 1.719 0.001 F2R 2.169 <.001FAM171B 1.430 0.044 FAP 1.993 0.002 FCGR3A 2.099 <.001 FN1 1.537 0.024GPR68 1.520 0.018 GREM1 1.942 <.001 IFI30 1.482 0.048 IGFBP3 1.513 0.027INHBA 3.060 <.001 KIF4A 1.355 0.001 KLK14 1.187 0.004 LAPTM5 1.613 0.006LTBP2 2.018 <.001 MMP11 1.869 <.001 MYBL2 1.737 0.013 NEK2 1.445 0.028NOX4 2.049 <.001 OLFML2B 1.497 0.023 PLK1 1.603 0.006 POSTN 2.585 <.001PPFIA3 1.502 0.012 PTK6 1.527 0.009 PTTG1 1.382 0.029 RAD51 1.304 0.031RGS7 1.251 <.001 RRM2 1.515 <.001 SAT1 1.607 0.004 SDC1 1.710 0.007SESN3 1.399 0.045 SFRP4 2.384 <.001 SHMT2 1.949 0.003 SPARC 2.249 <.001STMN1 1.748 0.021 SULF1 1.803 0.004 THBS2 2.576 <.001 THY1 1.908 0.001TK1 1.394 0.004 TOP2A 2.119 <.001 TPX2 2.074 0.042 UBE2C 1.598 <.001UGT2B15 1.363 0.016 UHRF1 1.642 0.001 ZWINT 1.570 0.010

TABLE 12B Table 12B Genes significantly (p < 0.05) associated withprostate cancer specific survival (PCSS) in the Primary Gleason PatternHR < 1.0 (Increased expression is positively associated with goodprognosis) Official Symbol HR p-value AAMP 0.649 0.040 ABCA5 0.777 0.015ABCG2 0.715 0.037 ACOX2 0.673 0.016 ADH5 0.522 <.001 ALDH1A2 0.561 <.001AMACR 0.693 0.029 AMPD3 0.750 0.049 ANPEP 0.531 <.001 ATXN1 0.640 0.011AXIN2 0.657 0.002 AZGP1 0.617 <.001 BDKRB1 0.553 0.032 BIN1 0.658 <.001BTRC 0.716 0.011 C7 0.531 <.001 CADM1 0.646 0.015 CASP7 0.538 0.029 CCNH0.674 0.001 CD164 0.606 <.001 CD44 0.687 0.016 CDK3 0.733 0.039 CHN10.653 0.014 COL6A1 0.681 0.015 CSF1 0.675 0.019 CSRP1 0.711 0.007 CXCL120.650 0.015 CYP3A5 0.507 <.001 CYR61 0.569 0.007 DLGAP1 0.654 0.004 DNM30.692 0.010 DPP4 0.544 <.001 DPT 0.543 <.001 DUSP1 0.660 0.050 DUSP60.699 0.033 EGR1 0.490 <.001 EGR3 0.561 <.001 EIF5 0.720 0.035 ERBB30.739 0.042 FAAH 0.636 0.010 FAM107A 0.541 <.001 FAM13C 0.526 <.001 FAS0.689 0.030 FGF10 0.657 0.024 FKBP5 0.699 0.040 FLNC 0.742 0.036 FOS0.556 0.005 FOXQ1 0.666 0.007 GADD45B 0.554 0.002 GDF15 0.659 0.009 GHR0.683 0.027 GPM6B 0.666 0.005 GSN 0.646 0.006 GSTM1 0.672 0.006 GSTM20.514 <.001 HGD 0.771 0.039 HIRIP3 0.730 0.013 HK1 0.778 0.048 HLF 0.581<.001 HNF1B 0.643 0.013 HSD17B10 0.742 0.029 IER3 0.717 0.049 IGF1 0.612<.001 IGFBP6 0.578 0.003 IL2 0.528 0.010 IL6ST 0.574 <.001 IL8 0.5400.001 ING5 0.688 0.015 ITGA6 0.710 0.005 ITGA7 0.676 0.033 JUN 0.5060.001 KIT 0.628 0.047 KLK1 0.523 0.002 KLK2 0.581 <.001 KLK3 0.676 <.001KRT15 0.684 0.005 KRT18 0.536 <.001 KRT5 0.673 0.004 KRT8 0.613 0.006LAMB3 0.740 0.027 LGALS3 0.678 0.007 MGST1 0.640 0.002 MPPED2 0.629<.001 MTSS1 0.705 0.041 MYBPC1 0.534 <.001 NCAPD3 0.519 <.001 NFAT50.536 <.001 NRG1 0.467 0.007 OLFML3 0.646 0.001 OMD 0.630 0.006 OR51E20.762 0.017 PAGE4 0.518 <.001 PCA3 0.581 <.001 PGF 0.705 0.038 PPAP2B0.568 <.001 PPP1R12A 0.694 0.017 PRIMA1 0.678 0.014 PRKCA 0.632 0.001PRKCB 0.692 0.028 PROM1 0.393 0.017 PTEN 0.689 0.002 PTGS2 0.611 0.004PTH1R 0.629 0.031 RAB27A 0.721 0.046 RND3 0.678 0.029 RNF114 0.714 0.035SDHC 0.590 <.001 SERPINA3 0.710 0.050 SH3RF2 0.570 0.005 SLC22A3 0.517<.001 SMAD4 0.528 <.001 SMO 0.751 0.026 SRC 0.667 0.004 SRD5A2 0.488<.001 STAT5B 0.700 0.040 SVIL 0.694 0.024 TFF3 0.701 0.045 TGFB1I1 0.6700.029 TGFB2 0.646 0.010 TNFRSF10B 0.685 0.014 TNFSF10 0.532 <.001 TPM20.623 0.005 TRO 0.767 0.049 TUBB2A 0.613 0.003 VEGFB 0.780 0.034 ZFP360.576 0.001 ZNF827 0.644 0.014

Analysis of gene expression and upgrading/upstaging was based onunivariate ordinal logistic regression models using weighted maximumlikelihood estimators for each gene in the gene list (727 test genes and5 reference genes). P-values were generated using a Wald test of thenull hypothesis that the odds ratio (OR) is one. Both unadjustedp-values and the q-value (smallest FDR at which the hypothesis test inquestion is rejected) were reported. Un-adjusted p-values <0.05 wereconsidered statistically significant. Since two tumor specimens wereselected for each patient, this analysis was performed using the 2specimens from each patient as follows: (1) analysis using the primaryGleason pattern specimen from each patient (Specimens A1 and B2 asdescribed in Table 2); and (2) analysis using the highest Gleasonpattern specimen from each patient (Specimens A1 and B1 as described inTable 2). 200 genes were found to be significantly associated (p<0.05)with upgrading/upstaging in the primary Gleason pattern sample (PGP) and203 genes were found to be significantly associated (p<0.05) withupgrading/upstaging in the highest Gleason pattern sample (HGP).

Tables 13A and 13B provide genes significantly associated (p<0.05),positively or negatively, with upgrading/upstaging in the primary and/orhighest Gleason pattern. Increased expression of genes in Table 13A ispositively associated with higher risk of upgrading/upstaging (poorprognosis), while increased expression of genes in Table 13B isnegatively associated with risk of upgrading/upstaging (good prognosis).

TABLE 13A Table 13A Genes significantly (p < 0.05) associated withupgrading/upstaging in the Primary Gleason Pattern (PGP) and HighestGleason Pattern (HGP) OR > 1.0 (Increased expression is positivelyassociated with higher risk of upgrading/upstaging (poor prognosis)) PGPHGP Gene OR p-value OR p-value ALCAM 1.52 0.0179 1.50 0.0184 ANLN 1.360.0451 . . APOE 1.42 0.0278 1.50 0.0140 ASPN 1.60 0.0027 2.06 0.0001AURKA 1.47 0.0108 . . AURKB . . 1.52 0.0070 BAX . . 1.48 0.0095 BGN 1.580.0095 1.73 0.0034 BIRC5 1.38 0.0415 . . BMP6 1.51 0.0091 1.59 0.0071BUB1 1.38 0.0471 1.59 0.0068 CACNA1D 1.36 0.0474 1.52 0.0078 CASP7 . .1.32 0.0450 CCNE2 1.54 0.0042 . . CD276 . . 1.44 0.0265 CDC20 1.350.0445 1.39 0.0225 CDKN2B . . 1.36 0.0415 CENPF 1.43 0.0172 1.48 0.0102CLTC 1.59 0.0031 1.57 0.0038 COL1A1 1.58 0.0045 1.75 0.0008 COL3A1 1.450.0143 1.47 0.0131 COL8A1 1.40 0.0292 1.43 0.0258 CRISP3 . . 1.40 0.0256CTHRC1 . . 1.56 0.0092 DBN1 1.43 0.0323 1.45 0.0163 DIAPH1 1.51 0.00881.58 0.0025 DICER1 . . 1.40 0.0293 DIO2 . . 1.49 0.0097 DVL1 . . 1.530.0160 F2R 1.46 0.0346 1.63 0.0024 FAP 1.47 0.0136 1.74 0.0005 FCGR3A .. 1.42 0.0221 HPN . . 1.36 0.0468 HSD17B4 . . 1.47 0.0151 HSPA8 1.650.0060 1.58 0.0074 IL11 1.50 0.0100 1.48 0.0113 IL1B 1.41 0.0359 . .INHBA 1.56 0.0064 1.71 0.0042 KHDRBS3 1.43 0.0219 1.59 0.0045 KIF4A . .1.50 0.0209 KPNA2 1.40 0.0366 . . KRT2 . . 1.37 0.0456 KRT75 . . 1.440.0389 MANF . . 1.39 0.0429 MELK 1.74 0.0016 . . MKI67 1.35 0.0408 . .MMP11 . . 1.56 0.0057 NOX4 1.49 0.0105 1.49 0.0138 PLAUR 1.44 0.0185 . .PLK1 . . 1.41 0.0246 PTK6 . . 1.36 0.0391 RAD51 . . 1.39 0.0300 RAF1 . .1.58 0.0036 RRM2 1.57 0.0080 . . SESN3 1.33 0.0465 . . SFRP4 2.33<0.0001   2.51 0.0015 SKIL 1.44 0.0288 1.40 0.0368 SOX4 1.50 0.0087 1.590.0022 SPINK1 1.52 0.0058 . . SPP1 . . 1.42 0.0224 THBS2 . . 1.36 0.0461TK1 . . 1.38 0.0283 TOP2A 1.85 0.0001 1.66 0.0011 TPD52 1.78 0.0003 1.640.0041 TPX2 1.70 0.0010 . . UBE2G1 1.38 0.0491 . . UBE2T 1.37 0.04251.46 0.0162 UHRF1 . . 1.43 0.0164 VCPIP1 . . 1.37 0.0458

TABLE 13B Table 13B Genes significantly (p < 0.05) associated withupgrading/upstaging in the Primary Gleason Pattern (PGP) and HighestGleason Pattern (HGP) OR < 1.0 (Increased expression is negativelyassociated with higher risk of upgrading/upstaging (good prognosis)) PGPHGP Gene OR p-value OR p-value ABCC3 . . 0.70 0.0216 ABCC8 0.66 0.0121 .. ABCG2 0.67 0.0208 0.61 0.0071 ACE . . 0.73 0.0442 ACOX2 0.46 0.00000.49 0.0001 ADH5 0.69 0.0284 0.59 0.0047 AIG1 . . 0.60 0.0045 AKR1C1 . .0.66 0.0095 ALDH1A2 0.36 <0.0001   0.36 <0.0001   ALKBH3 0.70 0.02810.61 0.0056 ANPEP . . 0.68 0.0109 ANXA2 0.73 0.0411 0.66 0.0080 APC . .0.68 0.0223 ATXN1 . . 0.70 0.0188 AXIN2 0.60 0.0072 0.68 0.0204 AZGP10.66 0.0089 0.57 0.0028 BCL2 . . 0.71 0.0182 BIN1 0.55 0.0005 . . BTRC0.69 0.0397 0.70 0.0251 C7 0.53 0.0002 0.51 <0.0001   CADM1 0.57 0.00120.60 0.0032 CASP1 0.64 0.0035 0.72 0.0210 CAV1 0.64 0.0097 0.59 0.0032CAV2 . . 0.58 0.0107 CD164 . . 0.69 0.0260 CD82 0.67 0.0157 0.69 0.0167CDH1 0.61 0.0012 0.70 0.0210 CDK14 0.70 0.0354 . . CDK3 . . 0.72 0.0267CDKN1C 0.61 0.0036 0.56 0.0003 CHN1 0.71 0.0214 . . COL6A1 0.62 0.01250.60 0.0050 COL6A3 0.65 0.0080 0.68 0.0181 CSRP1 0.43 0.0001 0.40 0.0002CTSB 0.66 0.0042 0.67 0.0051 CTSD 0.64 0.0355 . . CTSK 0.69 0.0171 . .CTSL1 0.72 0.0402 . . CUL1 0.61 0.0024 0.70 0.0120 CXCL12 0.69 0.02870.63 0.0053 CYP3A5 0.68 0.0099 0.62 0.0026 DDR2 0.68 0.0324 0.62 0.0050DES 0.54 0.0013 0.46 0.0002 DHX9 0.67 0.0164 . . DLGAP1 . . 0.66 0.0086DPP4 0.69 0.0438 0.69 0.0132 DPT 0.59 0.0034 0.51 0.0005 DUSP1 . . 0.670.0214 EDN1 . . 0.66 0.0073 EDNRA 0.66 0.0148 0.54 0.0005 EIF2C2 . .0.65 0.0087 ELK4 0.55 0.0003 0.58 0.0013 ENPP2 0.65 0.0128 0.59 0.0007EPHA3 0.71 0.0397 0.73 0.0455 EPHB2 0.60 0.0014 . . EPHB4 0.73 0.0418 .. EPHX3 . . 0.71 0.0419 ERCC1 0.71 0.0325 . . FAM107A 0.56 0.0008 0.550.0011 FAM13C 0.68 0.0276 0.55 0.0001 FAS 0.72 0.0404 . . FBN1 0.720.0395 . . FBXW7 0.69 0.0417 . . FGF10 0.59 0.0024 0.51 0.0001 FGF7 0.510.0002 0.56 0.0007 FGFR2 0.54 0.0004 0.47 <0.0001   FLNA 0.58 0.00360.50 0.0002 FLNC 0.45 0.0001 0.40 <0.0001   FLT4 0.61 0.0045 . . FOXO10.55 0.0005 0.53 0.0005 FOXP3 0.71 0.0275 0.72 0.0354 GHR 0.59 0.00740.53 0.0001 GNRH1 0.72 0.0386 . . GPM6B 0.59 0.0024 0.52 0.0002 GSN 0.650.0107 0.65 0.0098 GSTM1 0.44 <0.0001   0.43 <0.0001   GSTM2 0.42<0.0001   0.39 <0.0001   HLF 0.46 <0.0001   0.47 0.0001 HPS1 0.64 0.00690.69 0.0134 HSPA5 0.68 0.0113 . . HSPB2 0.61 0.0061 0.55 0.0004 HSPG20.70 0.0359 . . ID3 . . 0.70 0.0245 IGF1 0.45 <0.0001   0.50 0.0005 IGF20.67 0.0200 0.68 0.0152 IGFBP2 0.59 0.0017 0.69 0.0250 IGFBP6 0.49<0.0001   0.64 0.0092 IL6ST 0.56 0.0009 0.60 0.0012 ILK 0.51 0.0010 0.490.0004 ITGA1 0.58 0.0020 0.58 0.0016 ITGA3 0.71 0.0286 0.70 0.0221 ITGA5. . 0.69 0.0183 ITGA7 0.56 0.0035 0.42 <0.0001   ITGB1 0.63 0.0095 0.680.0267 ITGB3 0.62 0.0043 0.62 0.0040 ITPR1 0.62 0.0032 . . JUN 0.730.0490 0.68 0.0152 KIT 0.55 0.0003 0.57 0.0005 KLC1 . . 0.70 0.0248 KLK1. . 0.60 0.0059 KRT15 0.58 0.0009 0.45 <0.0001   KRT5 0.70 0.0262 0.590.0008 LAMA4 0.56 0.0359 0.68 0.0498 LAMB3 . . 0.60 0.0017 LGALS3 0.580.0007 0.56 0.0012 LRP1 0.69 0.0176 . . MAP3K7 0.70 0.0233 0.73 0.0392MCM3 0.72 0.0320 . . MMP2 0.66 0.0045 0.60 0.0009 MMP7 0.61 0.0015 0.650.0032 MMP9 0.64 0.0057 0.72 0.0399 MPPED2 0.72 0.0392 0.63 0.0042 MTA1. . 0.68 0.0095 MTSS1 0.58 0.0007 0.71 0.0442 MVP 0.57 0.0003 0.700.0152 MYBPC1 . . 0.70 0.0359 NCAM1 0.63 0.0104 0.64 0.0080 NCAPD3 0.670.0145 0.64 0.0128 NEXN 0.54 0.0004 0.55 0.0003 NFAT5 0.72 0.0320 0.700.0177 NUDT6 0.66 0.0102 . . OLFML3 0.56 0.0035 0.51 0.0011 OMD 0.610.0011 0.73 0.0357 PAGE4 0.42 <0.0001   0.36 <0.0001   PAK6 0.72 0.0335. . PCDHGB7 0.70 0.0262 0.55 0.0004 PGF 0.72 0.0358 0.71 0.0270 PLP20.66 0.0088 0.63 0.0041 PPAP2B 0.44 <0.0001   0.50 0.0001 PPP1R12A 0.450.0001 0.40 <0.0001   PRIMA1 . . 0.63 0.0102 PRKAR2B 0.71 0.0226 . .PRKCA 0.34 <0.0001   0.42 <0.0001   PRKCB 0.66 0.0120 0.49 <0.0001  PROM1 0.61 0.0030 . . PTEN 0.59 0.0008 0.55 0.0001 PTGER3 0.67 0.0293 .. PTH1R 0.69 0.0259 0.71 0.0327 PTK2 0.75 0.0461 . . PTK2B 0.70 0.02440.74 0.0388 PYCARD 0.73 0.0339 0.67 0.0100 RAD9A 0.64 0.0124 . . RARB0.67 0.0088 0.65 0.0116 RGS10 0.70 0.0219 . . RHOB . . 0.72 0.0475 RND3. . 0.67 0.0231 SDHC 0.72 0.0443 . . SEC23A 0.66 0.0101 0.53 0.0003SEMA3A 0.51 0.0001 0.69 0.0222 SH3RF2 0.55 0.0002 0.54 0.0002 SLC22A30.48 0.0001 0.50 0.0058 SMAD4 0.49 0.0001 0.50 0.0003 SMARCC2 0.590.0028 0.65 0.0052 SMO 0.60 0.0048 0.52 <0.0001   SORBS1 0.56 0.00240.48 0.0002 SPARCL1 0.43 0.0001 0.50 0.0001 SRD5A2 0.26 <0.0001   0.31<0.0001   ST5 0.63 0.0103 0.52 0.0006 STAT5A 0.60 0.0015 0.61 0.0037STAT5B 0.54 0.0005 0.57 0.0008 SUMO1 0.65 0.0066 0.66 0.0320 SVIL 0.520.0067 0.46 0.0003 TGFB1I1 0.44 0.0001 0.43 0.0000 TGFB2 0.55 0.00070.58 0.0016 TGFB3 0.57 0.0010 0.53 0.0005 TIMP1 0.72 0.0224 . . TIMP20.68 0.0198 0.69 0.0206 TIMP3 0.67 0.0105 0.64 0.0065 TMPRSS2 . . 0.720.0366 TNFRSF10A 0.71 0.0181 . . TNFSF10 0.71 0.0284 . . TOP2B 0.730.0432 . . TP63 0.62 0.0014 0.50 <0.0001   TPM1 0.54 0.0007 0.52 0.0002TPM2 0.41 <0.0001   0.40 <0.0001   TPP2 0.65 0.0122 . . TRA2A 0.720.0318 . . TRAF3IP2 0.62 0.0064 0.59 0.0053 TRO 0.57 0.0003 0.51 0.0001VCL 0.52 0.0005 0.52 0.0004 VIM 0.65 0.0072 0.65 0.0045 WDR19 0.660.0097 . . WFDC1 0.58 0.0023 0.60 0.0026 ZFHX3 0.69 0.0144 0.62 0.0046ZNF827 0.62 0.0030 0.53 0.0001

Example 3 Identification of MicroRNAs Associated with ClinicalRecurrence and Death Due to Prostate Cancer

MicroRNAs function by binding to portions of messenger RNA (mRNA) andchanging how frequently the mRNA is translated into protein. They canalso influence the turnover of mRNA and thus how long the mRNA remainsintact in the cell. Since microRNAs function primarily as an adjunct tomRNA, this study evaluated the joint prognostic value of microRNAexpression and gene (mRNA) expression. Since the expression of certainmicroRNAs may be a surrogate for expression of genes that are not in theassessed panel, we also evaluated the prognostic value of microRNAexpression by itself.

Patients and Samples

Samples from the 127 patients with clinical recurrence and 374 patientswithout clinical recurrence after radical prostatectomy described inExample 2 were used in this study. The final analysis set comprised 416samples from patients in which both gene expression and microRNAexpression were successfully assayed. Of these, 106 patients exhibitedclinical recurrence and 310 did not have clinical recurrence. Tissuesamples were taken from each prostate sample representing (1) theprimary Gleason pattern in the sample, and (2) the highest Gleasonpattern in the sample. In addition, a sample of histologicallynormal-appearing tissue adjacent to the tumor (NAT) was taken. Thenumber of patients in the analysis set for each tissue type and thenumber of them who experienced clinical recurrence or death due toprostate cancer are shown in Table 14.

TABLE 14 Number of Patients and Events in Analysis Set Deaths Due toPatients Clinical Recurrences Prostate Cancer Primary Gleason 416 106 36Pattern Tumor Tissue Highest Gleason 405 102 36 Pattern Tumor TissueNormal Adjacent 364 81 29 Tissue

Assay Method

Expression of 76 test microRNAs and 5 reference microRNAs weredetermined from RNA extracted from fixed paraffin-embedded (FPE) tissue.MicroRNA expression in all three tissue type was quantified by reversetranscriptase polymerase chain reaction (RT-PCR) using the crossingpoint (C_(p)) obtained from the Taqman® MicroRNA Assay kit (AppliedBiosystems, Inc., Carlsbad, Calif.).

Statistical Analysis

Using univariate proportional hazards regression (Cox D R, Journal ofthe Royal Statistical Society, Series B 34:187-220, 1972), applying thesampling weights from the cohort sampling design, and using varianceestimation based on the Lin and Wei method (Lin and Wei, Journal of theAmerican Statistical Association 84:1074-1078, 1989), microRNAexpression, normalized by the average expression for the 5 referencemicroRNAs hsa-miR-106a, hsa-miR-146b-5p, hsa-miR-191, hsa-miR-19b, andhsa-miR-92a, and reference-normalized gene expression of the 733 genes(including the reference genes) discussed above, were assessed forassociation with clinical recurrence and death due to prostate cancer.Standardized hazard ratios (the proportional change in the hazardassociated with a change of one standard deviation in the covariatevalue) were calculated.

This analysis included the following classes of predictors:

1. MicroRNAs alone

2. MicroRNA-gene pairs Tier 1

3. MicroRNA-gene pairs Tier 2

4. MicroRNA-gene pairs Tier 3

5. All other microRNA-gene pairs Tier 4

The four tiers were pre-determined based on the likelihood (Tier 1representing the highest likelihood) that the gene-microRNA pairfunctionally interacted or that the microRNA was related to prostatecancer based on a review of the literature and existing microarray datasets.

False discovery rates (FDR) (Benjamini and Hochberg, Journal of theRoyal Statistical Society, Series B 57:289-300, 1995) were assessedusing Efron's separate class methodology (Efron, Annals of AppliedStatistics 2:197-223., 2008). The false discovery rate is the expectedproportion of the rejected null hypotheses that are rejected incorrectly(and thus are false discoveries). Efron's methodology allows separateFDR assessment (q-values) (Storey, Journal of the Royal StatisticalSociety, Series B 64:479-498, 2002) within each class while utilizingthe data from all the classes to improve the accuracy of thecalculation. In this analysis, the q-value for a microRNA ormicroRNA-gene pair can be interpreted as the empirical Bayes probabilitythat the microRNA or microRNA-gene pair identified as being associatedwith clinical outcome is in fact a false discovery given the data. Theseparate class approach was applied to a true discovery rate degree ofassociation (TDRDA) analysis (Crager, Statistics in Medicine 29:33-45,2010) to determine sets of microRNAs or microRNA-gene pairs that havestandardized hazard ratio for clinical recurrence or prostatecancer-specific death of at least a specified amount while controllingthe FDR at 10%. For each microRNA or microRNA-gene pair, a maximum lowerbound (MLB) standardized hazard ratio was computed, showing the highestlower bound for which the microRNA or microRNA-gene pair was included ina TDRDA set with 10% FDR. Also calculated was an estimate of the truestandardized hazard ratio corrected for regression to the mean (RM) thatoccurs in subsequent studies when the best predictors are selected froma long list (Crager, 2010 above). The RM-corrected estimate of thestandardized hazard ratio is a reasonable estimate of what could beexpected if the selected microRNA or microRNA-gene pair were studied ina separate, subsequent study.

These analyses were repeated adjusting for clinical and pathologycovariates available at the time of patient biopsy: biopsy Gleasonscore, baseline PSA level, and clinical T-stage (T1-T2A vs. T2B or T2C)to assess whether the microRNAs or microRNA-gene pairs have predictivevalue independent of these clinical and pathology covariates.

Results

The analysis identified 21 microRNAs assayed from primary Gleasonpattern tumor tissue that were associated with clinical recurrence ofprostate cancer after radical prostatectomy, allowing a false discoveryrate of 10% (Table 15). Results were similar for microRNAs assessed fromhighest Gleason pattern tumor tissue (Table 16), suggesting that theassociation of microRNA expression with clinical recurrence does notchange markedly depending on the location within a tumor tissue sample.No microRNA assayed from normal adjacent tissue was associated with therisk of clinical recurrence at a false discovery rate of 10%. Thesequences of the microRNAs listed in Tables 15-21 are shown in Table B.

TABLE 15 MicroRNAs Associated with Clinical Recurrence of ProstateCancer Primary Gleason Pattern Tumor Tissue Absolute Standardized HazardRatio 95% Max. Lower RM- q-value^(a) Direction Uncorrected ConfidenceBound Corrected MicroRNA p-value (FDR) of Association^(b) EstimateInterval @10% FDR Estimate^(c) hsa-miR-93 <0.0001 0.0% (+) 1.79 (1.38,2.32) 1.19 1.51 hsa-miR-106b <0.0001 0.1% (+) 1.80 (1.38, 2.34) 1.191.51 hsa-miR-30e-5p <0.0001 0.1% (−) 1.63 (1.30, 2.04) 1.18 1.46hsa-miR-21 <0.0001 0.1% (+) 1.66 (1.31, 2.09) 1.18 1.46 hsa-miR-133a<0.0001 0.1% (−) 1.72 (1.33, 2.21) 1.18 1.48 hsa-miR-449a <0.0001 0.1%(+) 1.56 (1.26, 1.92) 1.17 1.42 hsa-miR-30a 0.0001 0.1% (−) 1.56 (1.25,1.94) 1.16 1.41 hsa-miR-182 0.0001 0.2% (+) 1.74 (1.31, 2.31) 1.17 1.45hsa-miR-27a 0.0002 0.2% (+) 1.65 (1.27, 2.14) 1.16 1.43 hsa-miR-2220.0006 0.5% (−) 1.47 (1.18, 1.84) 1.12 1.35 hsa-miR-103 0.0036 2.1% (+)1.77 (1.21, 2.61) 1.12 1.36 hsa-miR-1 0.0037 2.2% (−) 1.32 (1.10, 1.60)1.07 1.26 hsa-miR-145 0.0053 2.9% (−) 1.34 (1.09, 1.65) 1.07 1.27hsa-miR-141 0.0060 3.2% (+) 1.43 (1.11, 1.84) 1.07 1.29 hsa-miR-92a0.0104 4.8% (+) 1.32 (1.07, 1.64) 1.05 1.25 hsa-miR-22 0.0204 7.7% (+)1.31 (1.03, 1.64) 1.03 1.23 hsa-miR-29b 0.0212 7.9% (+) 1.36 (1.03,1.76) 1.03 1.24 hsa-miR-210 0.0223 8.2% (+) 1.33 (1.03, 1.70) 1.00 1.23hsa-miR-486-5p 0.0267 9.4% (−) 1.25 (1.00, 1.53) 1.00 1.20 hsa-miR-19b0.0280 9.7% (−) 1.24 (1.00, 1.50) 1.00 1.19 hsa-miR-205 0.0289 10.0% (−)1.25 (1.00, 1.53) 1.00 1.20 ^(a)The q-value is the empirical Bayesprobability that the microRNA's association with clinical recurrence isa false discovery, given the data. ^(b)Direction of associationindicates where higher microRNA expression is associated with higher (+)or lower (−) risk of clinical recurrence. ^(c)RM: regression to themean.

TABLE 16 MicroRNAs Associated with Clinical Recurrence of ProstateCancer Highest Gleason Pattern Tumor Tissue Absolute Standardized HazardRatio 95% Max. Lower RM- q-value^(a) Direction Uncorrected ConfidenceBound Corrected MicroRNA p-value (FDR) of Association^(b) EstimateInterval @10% FDR Estimate^(c) hsa-miR-93 <0.0001 0.0% (+) 1.91 (1.48,2.47) 1.24 1.59 hsa-miR-449a <0.0001 0.0% (+) 1.75 (1.40, 2.18) 1.231.54 hsa-miR-205 <0.0001 0.0% (−) 1.53 (1.29, 1.81) 1.20 1.43hsa-miR-19b <0.0001 0.0% (−) 1.37 (1.19, 1.57) 1.15 1.32 hsa-miR-106b<0.0001 0.0% (+) 1.84 (1.39, 2.42) 1.22 1.51 hsa-miR-21 <0.0001 0.0% (+)1.68 (1.32, 2.15) 1.19 1.46 hsa-miR-30a 0.0005 0.4% (−) 1.44 (1.17,1.76) 1.13 1.33 hsa-miR-30e-5p 0.0010 0.6% (−) 1.37 (1.14, 1.66) 1.111.30 hsa-miR-133a 0.0015 0.8% (−) 1.57 (1.19, 2.07) 1.13 1.36 hsa-miR-10.0016 0.8% (−) 1.42 (1.14, 1.77) 1.11 1.31 hsa-miR-103 0.0021 1.1% (+)1.69 (1.21, 2.37) 1.13 1.37 hsa-miR-210 0.0024 1.2% (+) 1.43 (1.13,1.79) 1.11 1.31 hsa-miR-182 0.0040 1.7% (+) 1.48 (1.13, 1.93) 1.11 1.31hsa-miR-27a 0.0055 2.1% (+) 1.46 (1.12, 1.91) 1.09 1.30 hsa-miR-2220.0093 3.2% (−) 1.38 (1.08, 1.77) 1.08 1.27 hsa-miR-331 0.0126 3.9% (+)1.38 (1.07, 1.77) 1.07 1.26 hsa-miR-191* 0.0143 4.3% (+) 1.38 (1.06,1.78) 1.07 1.26 hsa-miR-425 0.0151 4.5% (+) 1.40 (1.06, 1.83) 1.07 1.26hsa-miR-31 0.0176 5.1% (−) 1.29 (1.04, 1.60) 1.05 1.22 hsa-miR-92a0.0202 5.6% (+) 1.31 (1.03, 1.65) 1.05 1.23 hsa-miR-155 0.0302 7.6% (−)1.32 (1.00, 1.69) 1.03 1.22 hsa-miR-22 0.0437 9.9% (+) 1.30 (1.00, 1.67)1.00 1.21 ^(a)The q-value is the empirical Bayes probability that themicroRNA's association with death due to prostate cancer is a falsediscovery, given the data. ^(b)Direction of association indicates wherehigher microRNA expression is associated with higher (+) or lower (−)risk of clinical recurrence. ^(c)RM: regression to the mean.

Table 17 shows microRNAs assayed from primary Gleason pattern tissuethat were identified as being associated with the risk ofprostate-cancer-specific death, with a false discovery rate of 10%.Table 18 shows the corresponding analysis for microRNAs assayed fromhighest Gleason pattern tissue. No microRNA assayed from normal adjacenttissue was associated with the risk of prostate-cancer-specific death ata false discovery rate of 10%.

TABLE 17 MicroRNAs Associated with Death Due to Prostate Cancer PrimaryGleason Pattern Tumor Tissue Absolute Standardized Hazard Ratio Max.Lower 95% Bound RM- q-value^(a) Direction Uncorrected Confidence @10%Corrected MicroRNA p-value (FDR) of Association^(b) Estimate IntervalFDR Estimate^(c) hsa-miR-30e-5p 0.0001 0.6% (−) 1.88 (1.37, 2.58) 1.151.46 hsa-miR-30a 0.0001 0.7% (−) 1.78 (1.33, 2.40) 1.14 1.44hsa-miR-133a 0.0005 1.2% (−) 1.85 (1.31, 2.62) 1.13 1.41 hsa-miR-2220.0006 1.4% (−) 1.65 (1.24, 2.20) 1.12 1.38 hsa-miR-106b 0.0024 2.7% (+)1.85 (1.24, 2.75) 1.11 1.35 hsa-miR-1 0.0028 3.0% (−) 1.43 (1.13, 1.81)1.08 1.30 hsa-miR-21 0.0034 3.3% (+) 1.63 (1.17, 2.25) 1.09 1.33hsa-miR-93 0.0044 3.9% (+) 1.87 (1.21, 2.87) 1.09 1.32 hsa-miR-26a0.0072 5.3% (−) 1.47 (1.11, 1.94) 1.07 1.29 hsa-miR-152 0.0090 6.0% (−)1.46 (1.10, 1.95) 1.06 1.28 hsa-miR-331 0.0105 6.5% (+) 1.46 (1.09,1.96) 1.05 1.27 hsa-miR-150 0.0159 8.3% (+) 1.51 (1.07, 2.10) 1.03 1.27hsa-miR-27b 0.0160 8.3% (+) 1.97 (1.12, 3.42) 1.05 1.25 ^(a)The q-valueis the empirical Bayes probability that the microRNA's association withdeath due to prostate cancer endpoint is a false discovery, given thedata. ^(b)Direction of association indicates where higher microRNAexpression is associated with higher (+) or lower (−) risk of death dueto prostate cancer. ^(c)RM: regression to the mean.

TABLE 18 MicroRNAs Associated with Death Due to Prostate Cancer HighestGleason Pattern Tumor Tissue Absolute Standardized Hazard Ratio Max.Lower Bound q-value^(a) Direction Uncorrected 95% Confidence @10%RM-Corrected MicroRNA p-value (FDR) of Association^(b) Estimate IntervalFDR Estimate^(c) hsa-miR-27b 0.0016 6.1% (+) 2.66 (1.45, 4.88) 1.07 1.32hsa-miR-21 0.0020 6.4% (+) 1.66 (1.21, 2.30) 1.05 1.34 hsa-miR-10a0.0024 6.7% (+) 1.78 (1.23, 2.59) 1.05 1.34 hsa-miR-93 0.0024 6.7% (+)1.83 (1.24, 2.71) 1.05 1.34 hsa-miR-106b 0.0028 6.8% (+) 1.79 (1.22,2.63) 1.05 1.33 hsa-miR-150 0.0035 7.1% (+) 1.61 (1.17, 2.22) 1.05 1.32hsa-miR-1 0.0104 9.0% (−) 1.52 (1.10, 2.09) 1.00 1.28 ^(a)The q-value isthe empirical Bayes probability that the microRNA's association withclinical endpoint is a false discovery, given the data. ^(b)Direction ofassociation indicates where higher microRNA expression is associatedwith higher (+) or lower (−) risk of death due to prostate cancer.^(c)RM: regression to the mean.

Table 19 and Table 20 shows the microRNAs that can be identified asbeing associated with the risk of clinical recurrence while adjustingfor the clinical and pathology covariates of biopsy Gleason score,baseline PSA level, and clinical T-stage. The distributions of thesecovariates are shown in FIG. 1. Fifteen (15) of the microRNAs identifiedin Table 15 are also present in Table 19, indicating that thesemicroRNAs have predictive value for clinical recurrence that isindependent of the Gleason score, baseline PSA, and clinical T-stage.

Two microRNAs assayed from primary Gleason pattern tumor tissue werefound that had predictive value for death due to prostate cancerindependent of Gleason score, baseline PSA, and clinical T-stage (Table21).

TABLE 19 MicroRNAs Associated with Clinical Recurrence of ProstateCancer Adjusting for Biopsy Gleason Score, Baseline PSA Level, andClinical T-Stage Primary Gleason Pattern Tumor Tissue AbsoluteStandardized Hazard Ratio Max. Lower 95% Bound RM- q-value^(a) DirectionUncorrected Confidence @10% Corrected MicroRNA p-value (FDR) ofAssociation^(b) Estimate Interval FDR Estimate^(c) hsa-miR-30e-5p<0.0001 0.0% (−) 1.80 (1.42, 2.27) 1.23 1.53 hsa-miR-30a <0.0001 0.0%(−) 1.75 (1.40, 2.19) 1.22 1.51 hsa-miR-93 <0.0001 0.1% (+) 1.70 (1.32,2.20) 1.19 1.44 hsa-miR-449a 0.0001 0.1% (+) 1.54 (1.25, 1.91) 1.17 1.39hsa-miR-133a 0.0001 0.1% (−) 1.58 (1.25, 2.00) 1.17 1.39 hsa-miR-27a0.0002 0.1% (+) 1.66 (1.28, 2.16) 1.17 1.41 hsa-miR-21 0.0003 0.2% (+)1.58 (1.23, 2.02) 1.16 1.38 hsa-miR-182 0.0005 0.3% (+) 1.56 (1.22,1.99) 1.15 1.37 hsa-miR-106b 0.0008 0.5% (+) 1.57 (1.21, 2.05) 1.15 1.36hsa-miR-222 0.0028 1.1% (−) 1.39 (1.12, 1.73) 1.11 1.28 hsa-miR-1030.0048 1.7% (+) 1.69 (1.17, 2.43) 1.13 1.32 hsa-miR-486-5p 0.0059 2.0%(−) 1.34 (1.09, 1.65) 1.09 1.25 hsa-miR-1 0.0083 2.7% (−) 1.29 (1.07,1.57) 1.07 1.23 hsa-miR-141 0.0088 2.8% (+) 1.43 (1.09, 1.87) 1.09 1.27hsa-miR-200c 0.0116 3.4% (+) 1.39 (1.07, 1.79) 1.07 1.25 hsa-miR-1450.0201 5.1% (−) 1.27 (1.03, 1.55) 1.05 1.20 hsa-miR-206 0.0329 7.2% (−)1.40 (1.00, 1.91) 1.05 1.23 hsa-miR-29b 0.0476 9.4% (+) 1.30 (1.00,1.69) 1.00 1.20 ^(a)The q-value is the empirical Bayes probability thatthe microRNA's association with clinical recurrence is a falsediscovery, given the data. ^(b)Direction of association indicates wherehigher microRNA expression is associated with higher (+) or lower (−)risk of clinical recurrence. ^(c)RM: regression to the mean.

TABLE 20 MicroRNAs Associated with Clinical Recurrence of ProstateCancer Adjusting for Biopsy Gleason Score, Baseline PSA Level, andClinical T-Stage Highest Gleason Pattern Tumor Tissue AbsoluteStandardized Hazard Ratio Max. Lower 95% Bound RM- q-value^(a) DirectionUncorrected Confidence @10% Corrected MicroRNA p-value (FDR) ofAssociation^(b) Estimate Interval FDR Estimate^(c) hsa-miR-30a <0.00010.0% (−) 1.62 (1.32, 1.99) 1.20 1.43 hsa-miR-30e-5p <0.0001 0.0% (−)1.53 (1.27, 1.85) 1.19 1.39 hsa-miR-93 <0.0001 0.0% (+) 1.76 (1.37,2.26) 1.20 1.45 hsa-miR-205 <0.0001 0.0% (−) 1.47 (1.23, 1.74) 1.18 1.36hsa-miR-449a 0.0001 0.1% (+) 1.62 (1.27, 2.07) 1.18 1.38 hsa-miR-106b0.0003 0.2% (+) 1.65 (1.26, 2.16) 1.17 1.36 hsa-miR-133a 0.0005 0.2% (−)1.51 (1.20, 1.90) 1.16 1.33 hsa-miR-1 0.0007 0.3% (−) 1.38 (1.15, 1.67)1.13 1.28 hsa-miR-210 0.0045 1.2% (+) 1.35 (1.10, 1.67) 1.11 1.25hsa-miR-182 0.0052 1.3% (+) 1.40 (1.10, 1.77) 1.11 1.26 hsa-miR-4250.0066 1.6% (+) 1.48 (1.12, 1.96) 1.12 1.26 hsa-miR-155 0.0073 1.8% (−)1.36 (1.09, 1.70) 1.10 1.24 hsa-miR-21 0.0091 2.1% (+) 1.42 (1.09, 1.84)1.10 1.25 hsa-miR-222 0.0125 2.7% (−) 1.34 (1.06, 1.69) 1.09 1.23hsa-miR-27a 0.0132 2.8% (+) 1.40 (1.07, 1.84) 1.09 1.23 hsa-miR-191*0.0150 3.0% (+) 1.37 (1.06, 1.76) 1.09 1.23 hsa-miR-103 0.0180 3.4% (+)1.45 (1.06, 1.98) 1.09 1.23 hsa-miR-31 0.0252 4.3% (−) 1.27 (1.00, 1.57)1.07 1.19 hsa-miR-19b 0.0266 4.5% (−) 1.29 (1.00, 1.63) 1.07 1.20hsa-miR-99a 0.0310 5.0% (−) 1.26 (1.00, 1.56) 1.06 1.18 hsa-miR-92a0.0348 5.4% (+) 1.31 (1.00, 1.69) 1.06 1.19 hsa-miR-146b-5p 0.0386 5.8%(−) 1.29 (1.00, 1.65) 1.06 1.19 hsa-miR-145 0.0787 9.7% (−) 1.23 (1.00,1.55) 1.00 1.15 ^(a)The q-value is the empirical Bayes probability thatthe microRNA's association with clinical clinical recurrence is a falsediscovery, given the data. ^(b)Direction of association indicates wherehigher microRNA expression is associated with higher (+) or lower (−)risk of clinical recurrence. ^(c) RM: regression to the mean.

TABLE 21 MicroRNAs Associated with Death Due to Prostate CancerAdjusting for Biopsy Gleason Score, Baseline PSA Level, and ClinicalT-Stage Primary Gleason Pattern Tumor Tissue Absolute StandardizedHazard Ratio Max. Lower 95% Bound RM- q-value^(a) Direction UncorrectedConfidence @10% Corrected MicroRNA p-value (FDR) of Association^(b)Estimate Interval FDR Estimate^(c) hsa-miR-30e-5p 0.0001 2.9% (−) 1.97(1.40, 2.78) 1.09 1.39 hsa-miR-30a 0.0002 3.3% (−) 1.90 (1.36, 2.65)1.08 1.38 ^(a)The q-value is the empirical Bayes probability that themicroRNA's association with clinical recurrence is a false discovery,given the data. ^(b)Direction of association indicates where highermicroRNA expression is associated with higher (+) or lower (−) risk ofclinical recurrence. ^(c)RM: regression to the mean.

Accordingly, the normalized expression levels of hsa-miR-93;hsa-miR-106b; hsa-miR-21; hsa-miR-449a; hsa-miR-182; hsa-miR-27a;hsa-miR-103; hsa-miR-141; hsa-miR-92a; hsa-miR-22; hsa-miR-29b;hsa-miR-210; hsa-miR-331; hsa-miR-191; hsa-miR-425; and hsa-miR-200c arepositively associated with an increased risk of recurrence; andhsa-miR-30e-5p; hsa-miR-133a; hsa-miR-30a; hsa-miR-222; hsa-miR-1;hsa-miR-145; hsa-miR-486-5p; hsa-miR-19b; hsa-miR-205; hsa-miR-31;hsa-miR-155; hsa-miR-206; hsa-miR-99a; and hsa-miR-146b-5p arenegatively associated with an increased risk of recurrence.

Furthermore, the normalized expression levels of hsa-miR-106b;hsa-miR-21; hsa-miR-93; hsa-miR-331; hsa-miR-150; hsa-miR-27b; andhsa-miR-10a are positively associated with an increased risk of prostatecancer specific death; and the normalized expression levels ofhsa-miR-30e-5p; hsa-miR-30a; hsa-miR-133a; hsa-miR-222; hsa-miR-1;hsa-miR-26a; and hsa-miR-152 are negatively associated with an increasedrisk of prostate cancer specific death.

Table 22 shows the number of microRNA-gene pairs that were grouped ineach tier (Tiers 1-4) and the number and percentage of those that werepredictive of clinical recurrence at a false discovery rate of 10%.

TABLE 22 Number of Pairs Predictive of Total Number of ClinicalRecurrence at False Tier MicroRNA-Gene Pairs Discovery Rate 10% (%) Tier1 80 46 (57.5%) Tier 2 719 591 (82.2%) Tier 3 3,850 2,792 (72.5%) Tier 454,724 38,264 (69.9%)

TABLE A SEQ SEQ SEQ SEQ Official Accession ID Forward ID Reverse ID IDSymbol: Number: NO Primer Sequence: NO Primer Sequence: NOProbe Sequence: NO Amplicon Sequence: AAMP NM_001087 1 GTGTGGCAGGTGGAC 2CTCCATCCACTCCAGG 3 CGCTTCAAAGGACC 4GTGTGGCAGGTGGACACTAAGGAGGAGGTCTGGTCCTTT ACTAA TCTC AGACCTCCTCGAAGCGGGAGACCTGGAGTGGATGGAG ABCA5 NM_172232 5 GGTATGGATCCCAAA 6CAGCCCGCTTTCTGTT 7 CACATGTGGCAGAG 8GGTATGGATCCCAAAGCCAAACAGCACATGTGGCGAGCA GCCA TTTA CAATTCGAACTATTCGAACTGCATTTAAAAACAGAAAGCGGGCT ABCD1 NM_000927 9 AAACACCACTGGAGC 10CAAGCCTGGAACCTAT 11 CAAGCCTGGAACCT 12AAACACCACTGGAGCATTGACTACCAGGCTCGCCAATGA ATTGA AGCC ATAGCCTGCTGCTCAAGTTAAAGGGGCTATAGGTTCCAG ABCC1 NM_004996 13 TCATGGTGCCCGTCA 14CGATTGTCTTTGCTCT 15 ACCTGATACGTCTT 16TCATGGTGCCCGTCAATGCTGTGATGGCGATGAAGACCA ATG TCATGTG GGTCTTCATCGCCAAGACGTATCAGGTGGCCCACATGAAGAGCAAAG T ABCC3 NM_003786 17 TCATCCTGGCGATCT18 CCGTTGAGTGGAATCA 19 TCTGTCCTGGCTGG 20TCATCCTGGCGATCTACTTCCTCTGGCAGAACCTAGGTC ACTTCCT GCAA AGTCGCTTTCATCCTCTGTCCTGGCTGGAGTCGCTTTCATGGTCTTGCTGA TTCCACTCAACGG ABCC4 NM_005845 21AGCGCCTGGAATCTA 22 AGAGCCCCTGGAGAGA 23 CGGAGTCCAGTGTT 24AGCGCCTGGAATCTACAACTCGGAGTCCAGTGTTTTCCC CAACT AGAT TTCCCACTTAACTTATCATCTTCTCTCCAGGGGCTCT ABCC8 NM_000351 25 CGTCTGTCACTGTGG 26TGATCCGGTTTAGCAG 27 AGTCTCTTGGCCAC 28CGTCTGTCACTGTGGAGTGGACAGGGCTGAAGGTGGCCA AGTGG GC CTTCAGCCCTAGAGACTGCACCGCAGCCTGCTAAACCGGATCA ABCG2 NM_004827 29 GGTCTCAACGGCATC 30CTTGGATCTTTCCTTG 31 ACGAAGATTTGCCT 32GGTCTCAACGCCATCCTGGGACCCACAGGTGGAGGCAAA CTG CAGC CCACCTGTGGTCTTCGTTATTAGATGTCTTAGCTGCAAGGAAAG ABHD2 NM_007011 33 GTAGTGGGTCTGCAT 34TGAGGGTTGGCACTCA 35 CAGGTGGCTCCTTT 36GTAGTGGGTCTGCATGGATGTTTCAGGGATCAAAGGAGC GGATGT GG GATCCCTGACACCTGGGCGCCTGAGTGCCAACCCTCA ACE NM_000789 37 CCGCTGTACGAGGAT 38CCGTGTCTGTGAAGCC 39 TGCCCTCAGCAATG 40CCGCTGTACGAGGATTTCACTGCCCTCAGCAATGAAGCC TTCA GT AAGCCTACAATACAAGCAGGACGGCTTCACAGACACGG ACOX2 NM_003500 41 ATGGAGGTGCCCAGA 42ACTCCGGGTAACTGTG 43 TGCTCTCAACTTTC 44ATGGAGGTGCCCAGAACACTGCACTCCGCAGGAAAGTTG ACAC GATG CTGCGGAGTGAGAGCATCATCCACAGTTACCCGGAGT ACTR2 NM_005722 45 ATCCGCATTGAAGAC 46ATCCGCTAGAACTGCA 47 CCCGCAGAAAGCAC 48ATCCGCATTGAAGACCCACCCCGCAGAAAGCACATGGTA CCA CCAC ATGGTATTCCTTCCTGGGTGGTGCAGTTCTAGCGGAT ADAM15 NM_003815 49 GGCGGGATGTGGT 50ATTTCTGGGCCTCCG 51 TCAGCCACAATCAC 52GGCGGGATGTGGTAACAGAGACCAAGACTGTGGAGT CAACTC ADAMTS1 NM_006988 53GGACAGGTGCAAGCT 54 ATCTACAACCTTGGGC 55 CAAGCCAAAGGCAT 56GGACAGGTGCAAGCTCATCTGCCAAGCCAAAGGCATTGG CATCTG TGCAA TGGCTACTTCTTCGCTACTTCTTCGTTTTGCAGCCCAAGGTTGTAGAT ADH5 NM_000671 57 ATGCTGTCATCATT 58CTGCTTCCTTTCCCTT 59 TGTCTGCCCATTAT 60ATGCTGTCATCATTGTCACGGTTTGTCTGCCCATTAT CTTCAT AFAP1 NM_198595 61GATGTCCATCCTT 62 CAACCCTGATGCCTG 63 CCTCCAGTGCTGTG 64GATGTCCATCCTTGAAACAGCCTCTTCTGGGAACACA TTCCCA AGTR1 NM_000685 65AGCATTGATCGAT 66 CTACAAGCATTGTGC 67 ATTGTTCACCCAAT 68AGCATTGATCGATACCTGGCTATTGTTCACCCAATGA GAAGTC AGTR2 NM_000686 69ACTGGCATAGGAA 70 ATTGACTGGGTCTCTT 71 CCACCCAGACCCCA 72ACTGGCATAGGAAATGGTATCCAGAATGGAATTTTG TGTAGC AIG1 NM_016108 73CGACGGTTCTGCC 74 TGCTCCTGCTGGGAT 75 AATCGAGATGAGGA 76CGACGGTTCTGCCCTTTATATTAATCGAGATGAGGAC CATCGC AKAP1 NM_003488 77TGTGGTTGGAGAT 78 GTCTACCCACTGGGC 79 CTCCACCAGGGACC 80TGTGGTTGGAGATGAAGTGGTGTTGATAAACCGGTC GGTTTA AKR1C1 BC040210 81GTGTGTGAAGCTG 82 CTCTGCAGGCGCATA 83 CCAAATCCCAGGAC 84GTGTGTGAAGCTGAATGATGGTCACTTCATGCCTGTG AGGCAT AKR1C3 NM_003739 85GCTTTGCCTGATGTC 86 GTCCAGTCACCGGCAT 87 TGCGTCACCATCCA 88GCTTTGCCTGATGTCTACCAGAAGCCCTGTGTGTGGATG TACCAGAA AGAGA CACACAGGGGTGACGCAGAGGACGTCTCTATGCCGGTGACTGG AKT1 NM_005163 89 CGCTTCTATGGCG 90TCCCGGTACACCACG 91 CAGCCCTGGACTAC 92CGCTTCTATGGCGCTGAGATTGTGTCAGCCCTGGACT CTGCAC AKT2 NM_001626 93TCCTGCCACCCTTC 94 GGCGGTAAATTCATC 95 CAGGTCACGTCCGA 96TCCTGCCACCCTTCAAACCTCAGGTCACGTCCGAGGT GGTCGA AKT3 NM_005465 97TTGTCTCTGCCTTGG 98 CCAGCATTAGATTCTC 99 TCACGGTACACAAT 100TTGTCTCTGCCTTGGACTATCTACATTCCGGAAAGATTG ACTATCTACA CAACTTGA CTTTCCGGATGTACCGTGATCTCAAGTTGGAGAATCTAATGCTG ALCAM NM_001627 101 GAGGAATATGGAA102 GTGGCGGAGATCAAG 103 CCAGTTCCTGCCGT 104GAGGAATATGGAATCCAAGGGGGCCAGTTCCTGCCG CTGCTC ALDH18A1 NM_002860 105GATGCAGCTGGAACC 106 CTCCAGCTCAGTGGGG 107 CCTGAAACTTGCAT 108GATGCAGCTGGAACCCAAGCTGCAGCAGGAGATGCAAGT CAA AA CTCCTGCTGCTTCAGGATGTTCCCCACTGAGCTGGAG ALDH1A NM_170696 109 CACGTCTGTCCCT 110GACCGTGGCTCAACT 111 TCTCTGTAGGGCCC 112CACGTCTGTCCCTCTCTGCTTTCTCTGTAGGGCCCAG AGCTCT ALKBH3 NM_139178 113TCGCTTAGTCTGC 114 TCTGAGCCCCAGTTTT 115 TAAACAGGGCAGTC 116TCGCTTAGTCTGCACCTCAACCGTGCGGAAAGTGACT ACTTTC ALOX12 NM_000697 117AGTTCCTCAATGG 118 AGCACTAGCCTGGAG 119 CATGCTGTTGAGAC 120AGTTCCTCAATGGTGCCAACCCCATGCTGTTGAGACG GCTCGA ALOX5 NM_000698 121GAGCTGCAGGACT 122 GAAGCCTGAGGACTT 123 CCGCATGCCGTACA 124GAGCTGCAGGACTTCGTGAACGATGTCTACGTGTAC CGTAGA AMACR NM_203382 125GTCTCTGGGCTGTCA 126 TGGGTATAAGATCCAG 127 TCCATGTGTTTGAT 128GTCTCTGGGCTGTCAGCTTTCCTTTCTCCATGTGTTTGA GCTTT AACTTGC TTCTCCTCAGGCTTTCTCCTCAGGCTGGTAGCAAGTTCTGGATCTTA AMPD3 NM_000480 129 TGGTTCATCCAGCAC130 CATAAATCCGGGGCAC 131 TACTCTCCCAACAT 132TGGTTCATCCAGCACAAGGTCTACTCTCCCAACATGCGC AAGG CT GCGCTGGATCTGGATCATCCAGGTGCCCCGGATTTATG ANGPT2 NM_001147 133 CCGTGAAAGCTGC 134TTGCAGTGGGAAGAA 135 AAGCTGACACAGCC 136CCGTGAAAGCTGCTCTGTAAAAGCTGACACAGCCCT CTCCCA ANLN NM_018685 137TGAAAGTCCAAAA 138 CAGAACCAAGGCTAT 139 CCAAAGAACTCGTG 140TGAAAGTCCAAAACCAGGAAAATTCCAAAGAACTCG TCCCTC ANPEP NM_001150 141CCACCTTGGACCAAA 142 TCTCAGCGTCACCTGG 143 CTCCCCAACACGCT 144CCACCTTGGACCAAAGTAAAGCGTGGAATCTTACCGCCT GTAAAGC TAGGA GAAACCCGCCCCAACACGCTGAAACCCGATTCCTACCGGG ANXA2 NM_004039 145 CAAGACACTAAGGGC 146CGTGTCGGGCTTCAGT 147 CCACCACACAGGTA 148CAAGACACTAAGGGCGACTACCAGAAAGCGCTGCTGTAC GACTACCA CAT CAGCAGCGCTCTGTGTGGTGGAGATGACTGAAGCCCGACACG APC NM_000038 149 GGACAGCAGGAAT 150ACCCACTCGATTTGTT 151 CATTGGCTCCCCGT 152GGACAGCAGGAATGTGTTTCTCCATACAGGTCACGG GACCTG APEX1 NM_001641 153GATGAAGCCTTTC 154 AGGTCTCCACACAGC 155 CTTTCGGGAAGCCA 156GATGAAGCCTTTCGCAAGTTCCTGAAGGGCCTGGCTT GGCCCT APOC1 NM_001645 157CCAGCCTGATAAA 158 CACTCTGAATCCTTGC 159 AGGACAGGACCTCC 160CCAGCCTGATAAAGGTCCTGCGGGCAGGACAGGACC CAACCA APOE NM_000041 161GCCTCAAGAGCTGGT 162 CCTGCACCTTCTCCAC 163 ACTGGCGCTGCATG 164GCCTCAAGAGCTGGTTCGAGCCCCTGGTGGAAGACATGC TCG CA TCTTCCACAGCGCCAGTGGGCCGGGCTGGTGGAGAAGGTGC APRT NM_000485 165 GAGGTCCTGGAGT 166AGGTGCCAGCTTCTC 167 CCTTAAGCGAGGTC 168GAGGTCCTGGAGTGCGTGAGCCTGGTGGAGCTGACC AGCTCC AQP2 NM_000486 169GTGTGGGTGCCAG 170 CCCTTCAGCCCTCTCA 171 CTCCTTCCCTTCCC 172GTGTGGGTGCCAGTCCTCCTCAGGAGAAGGGGAAGG CTTCTCC AR NM_000044 173CGACTTCACCGCA 174 TGACACAAGTGGGAC 175 ACCATGCCGCCAGG 176CAGCTTCACCGCACCTGATGTGTGGTACCCTGGCGG GTACCA ARF1 NM_001658 177CAGTAGAGATCCC 178 ACAAGCACATGGCTA 179 CTTGTCCTTGGGTC 180CAGTAGAGATCCCCGCAACTCGCTTGTCCTTGGGTCA ACCCTG ARHGAP29 NM_004815 181CACGGTCTCGTGGTG 182 CAGTTGCTTGCCCAGG 183 ATGCCAGACCCAGA 184CACGGTCTCGTGGTGAAGTCAATGCCAGACCCAGACAAA AAGT AC CAAAGCATCAGCATCAGCTTGTCCTGGGCAAGCAACTG ARHGD1 NM_001175 185 TGGTCCCTAGAAC 186TGATGGAGGATCAGA 187 TAAAACCGGGCTTT 188TGGTCCCTAGAACAAGAGGCTTAAAACCGGGCTTTC CACCCA ASAP2 NM_003887 189CGGCCCATCAGCT 190 CTCTGGCCAAAGATA 191 CTGGGCTCCAACCA 192CGGCCCATCAGCTTCTACCAGCTGGGCTCCAACCAG GCTTCA ASPN NM_017680 193TGGACTAATCTGT 194 AAACACCCTTCAACA 195 AGTATCACCCAGGG 196TGGACTAATCTGTGGGAGCAGTTTATTCCAGTATCAC TGCAGC ATM NM_000051 197TGCTTTCTACACAT 198 GTTGTGGATCGGCTC 199 CCAGCTGTCTTCGA 200TGCTTTCTACACATGTTCAGGGATTTTTCACCAGCTG CACTTC ATP5E NM_006886 201CCGCTTTCGCTAC 202 TGGGAGTATCGGATG 203 TCCAGCCTGTCTCC 204CCGCTTTCGCTACAGCATGGTGGCCTACTGGAGACA AGTAGG ATP5J NM_0010037 205GTCGACCGACTGAAA 206 CTCTACTTCCGGCCC 207 CTACCCGCCATCGC 208GTCGACCGACTGAAACGGCGGCCCATAATGCATTGCGAT 03 CGG TGG AATGCATTATGGCGGGTAGGCGTGTGGGGGCGGAGCCAGGGCC ATXN1 NM_000332 209 GATCGACTCCAGC 210GAACTGTATCACGGC 211 CGGGCTATGGCTGT 212GATCGACTCCAGCACCGTAGAGGATTGAAGACAG CTTCAA AURKA NM_003600 213CATCTTCCAGGAG 214 TCCGACCTTCAATCAT 215 CTCTGTGGCACCCT 216CATCTTCCAGGAGGACCACTCTCTGTGGCACCCTGGA GGACTA AURKB NM_004217 217AGCTGCAGAAGAG 218 GCATCTGCCAACTCC 219 TGACGAGCAGCGAA 220AGCTGCAGAAGAGCTGCACATTTGACGAGCAGCGAA CAGCC AXIN2 NM_004655 221GGCTATGTCTTTG 222 ATCCGTCAGCGCATC 223 ACCAGCGCCAACGA 224GGCTATGTCTTTGCACCAGCCACCAGCGCCAACGAC CAGTG AZGP1 NM_001185 225GAGGCCAGCTAGG 226 CAGGAAGGGCAGCTA 227 TCTGAGATCCCACA 228GAGGCCAGCTAGGAAGCAAGGGTTGGAGGCAATGTG TTGCCT BAD NM_032989 229GGGTCAGGGGCCT 230 CTGCTCACTCGGCTC 231 TGGGCCCAGAGCAT 232GGGTCAGGGGCCTCGAGATCGGGCTTGGGCCCAGAG GTTCCA BAG5 NM_001015049 233ACTCCTGCAATGAAC 234 ACAAACAGCTCCCCAC 235 ACACCGGATTTAGC 236ACTCCTGCAATGAACCCTGTTGACACCGGATTTAGCTCT CCTGT GA TCTTGTCGGCTGTCGGCCTTCGTGGGGAGCTGTTTGT BAK1 NM_001188 237 CCATTCCCACCATT 238GGGAACATAGACCCA 239 ACACCCCAGACGTC 240CCATTCCCACCATTCTACCTGAGGCCAGGACGTCTGG CTGGCC BAX NM_004324 241CCGCCGTGGACAC 242 TTGCCGTCAGAAAAC 243 TGCCACTCGGAAAA 244CCGCCGTGGACACAGACTCCCCCCGAGAGGTCTTTTT AGACCT BBC3 NM_014417 245CCTGGAGGGTCCTGT 246 CTAATTGGGCTCCATC 247 CATCATGGGACTCC 248CCTGGAGGGTCCTGTACAATCTCATCATGGGACTCCTGC ACAAT TCG TGCCCTTACCCCTTACCCAGGGGCCACAGAGCCCCCGAGATGGA BCL2 NM_000633 249 CAGATGGACCTAGTA250 CCTATGATTTAAGGGC 251 TTCCACGCCGAAGG 252CAGATGGACCTAGTACCCACTGAGATTTCCACGCCGAAG CCCACTGAGA ATTTTTCC ACAGCGATGACAGCGATGGGAAAAATGCCCTTAAATCATAG BDKRB1 NM_000710 253 GTGGCAGAAATCT 254GAAGGGCAAGCCCAA 255 ACCTGGCAGCCTCT 256GTGGCAGAAATCTACCTGGCCAACCTGGCAGCCTCT GATCTG BGN NM_001711 257GAGCTCCGCAAGG 258 CTTGTTGTTCACCAGG 259 CAAGGGTCTCCAGC 260GAGCTCCGCAAGGATGACTTCAAGGGTCTCCAGCAC ACCTCT BIK NM_001197 261ATTCCTATGGCTCTG 262 GGCAGGAGTGAATGGC 263 CCGGTTAACTGTGG 264ATTCCTATGGCTCTGCAATTGTCACCGGTTAACTGTGGC CAATTGTC TCTTC CCTGTGCCCCTGTGCCCAGGAAGAGCCATTCACTCCTGCC BIN1 NM_004305 265 CCTGCAAAAGGGAAC 266CGTGGTTGACTCTGAT 267 CTTCGCCTCCAGAT 268CCTGCAAAAGGGAACAAGAGCCCTTCGCCTCCAGATGGC AAGAG CTCG GGCTCCCTCCCCTGCCGCCACCCCCGAGATCAGAGTCAAC BIRC5 NM_001012271 269 TTCAGGTGGATGAGG270 CACACAGCAGTGGCAA 271 TCTGCCAGACGCTT 272TTCAGGTGGATGAGGAGACAGAATAGAGTGATAGGAAGC AGACA AAG CCTATCACTCTATTGTCTGGCAGATACTCCTTTTGCCACTGCTGTGTG C BMP6 NM_001718 273 GTGCAGACCTTGG274 CTTAGTTGGCGCACA 275 TGAACCCCGAGTAT 276GTGCAGACCTTGGTTCACCTTATGAACCCCGAGTATG GTCCCC BMPR1B NM_001203 277ACCACTTTGGCCA 278 GCGGTGTTTGTACCC 279 ATTCACATTACCAT 280ACCACTTTGGCCATCCCTGCATTTGGGGCCGTCTATGG AGCGGC BRCA1 NM_007294 281TCAGGGGGCTAGA 282 CCATTCCAGTTGATCT 283 CTATGGGCCCTTCA 284TCAGGGGGCTAGAAATCTGTTGCTATGGGCCCTTCAC CCAACA BRCA2 NM_000059 285AGTTCGTGCTTTG 286 AAGGTAAGCTGGGTC 287 CATTCTTCACTGCT 288AGTTCGTGCTTTGCAAGATGGTGCAGAGCTTTATGAA TCATAA BTG1 NM_001731 289GAGGTCCGAGCGA 290 AGTTATTTTCGAGAC 291 CGCTCGTCTCTTCC 292GAGGTCCGAGCGATGTGACCAGGCCGCCATCGCTCG TCTCTC BTG3 NM_006806 293CCATATCGCCCAA 294 CCAGTGATTCCGGTC 295 CATGGGTACCTCCT 296CCATATCGCCCAATTCCAGTGACATGGGTACCTCCTC CCTGGA BTRC NM_033637 297GTTGGGACACAGT 298 TGAAGCAGTCAGTTG 299 CAGTCGGCCCAGGA 300GTTGGGACACAGTTGGTCTGCAGTCGGCCCAGGACG CGGTCT BUB1 NM_004336 301CCGAGGTTAATCC 302 AAGACATGGCGCTCT 303 TGCTGGGAGCCTAC 304CCGAGGTTAATCCAGCACGTATGGGGCCAAGTGTAG ACTTGG C7 NM_000587 305ATGTCTGAGTGTG 306 AGGCCTTATGCTGGT 307 ATGCTCTGCCCTCT 308ATGTCTGAGTGTGAGGCGGGCGCTCTGAGATGCAGA GCATCT CACNA1D NM_000720 309AGGACCCAGCTCCAT 310 CCTACATTCCGTGCC 311 CAGTACACTGGCGT 312AGGACCCAGCTCCATGTGCGTTCTCAGGGAATGGACGCC GTG ATTG CCATTCCCTGAGTGTACTGCCAATGGCACGGAATGTAGG CADM1 NM_014333 313 CCACCACCATCCT 314GATCCACTGCCCTGA 315 TCTTCACCTGCTCG 316CCACCACCATCCTTACCATCATCACAGATTCCCGAGC GGAATC CADPS NM_003716 317CAGCAAGGAGACT 318 GGTCCTCTTCTCCACG 319 CTCCTGGATGGCCA 320CAGCAAGGAGACTGTGCTGAGCTCCTGGATGGCCAA AATTTG CASP1 NM_001223 321AACTGGAGCTGAG 322 CATCTACGCTGTACC 323 TCACAGGCATGACA 324AACTGGAGCTGAGGTTGACATCACAGGCATGACAAT ATGCTG CASP3 NM_032991 325TGAGCCTGAGCAG 326 CCTTCCTGCGTGGTCC 327 TCAGCCTGTTCCAT 328TGAGCCTGAGCAGAGACATGACTCAGCCTGTTCCAT GAAGGC CASP7 NM_033338 329GCAGCGCCGAGAC 330 AGTCTCTCTCCGTCGC 331 CTTTCGCTAAAGGG 332GCAGCGCCGAGACTTTAGTTTCGCTTTCGCTAAAGG GCCCCA CAV1 NM_001753 333GTGGCTCAACATT 334 CAATGGCCTCCATTTT 335 ATTTCAGCTGATCA 336GTGGCTCAACATTGTGTTCCCATTTCAGCTGATCAGT GTGGGC CAV2 NM_198212 337CTTCCCTGGGACG 338 CTCCTGGTCACCCTTC 339 CCCGTACTGTCATG 340CTTCCCTGGGACGACTTGCCAGCTCTGAGGCATGAC CCTCAG CCL2 NM_002982 341CGCTCAGCCAGATGC 342 GCACTGAGATCTTCCT 343 TGCCCCAGTCACCT 344CGCTCAGCCAGATGCAATCAATGCCCCAGTCACCTGCTG AATC ATTGGTGAA GCTGTTATTATAACTTCACCAATAGGAAGATCTCAGTGC CCL5 NM_002985 345 AGGTTCTGAGCTC 346ATGCTGACTTCCTTCC 347 ACAGAGCCCTGGCA 348AGGTTCTGAGCTCTGGCTTTGCCTTGGCTTTGCCAGG AAGCC CCNB1 NM_031996 349TTCAGGTTGTTGCAG 350 CATCTTCTTGGGCACA 351 TGTCTCCATTATGA 352TTCAGGTTGTTGCAGGAGACCATGTACATGACTGTCTCC GAGAC CAAT TCGGTTCATGCAATTATTGATCGGTTCATGCAGAATAATTGTGTGCC CCND1 NM_001758 353 GCATGTTCGTGGC354 CGGTGTAGATGCACA 355 AAGGAGACCATCCC 356GCATGTTCGTGGCCTCTAAGATGAAGGAGACCATCC CCTGAC CCNE2 NM_057749 357ATGCTGTGGCTCCTT 358 ACCCAAATTGTGATAT 359 TACCAAGCAACCTA 360ATGCTGTGGCTCCTTCCTAACTGGGGCTTTCTTGACATGT CCTAACT ACAAAAAGGTTCATGTCAAGAAAGC AGGTTGCTTGGTAATAACCTTTTTGTATATCACA CC CCNH NM_001239 361GAGATCTTCGGTG 362 CTGCAGACGAGAACC 363 CATCAGCGTCCTGG 364GAGATCTTCGGTGGGGGTACGGGTGTTTTACGCCAG CGTAAA CCR1 NM_001295 365TCCAAGACCCAAT 366 TCGTAGGCTTTCGTG 367 ACTCACCACACCTG 368TCCAAGACCCAATGGGAATTCACTCACCACACCTGC CAGCCT CD164 NM_006016 369CAACCTGTGCGAA 370 ACACCCAAGACCAGGC 371 CCTCCAATGAAACT 372CAACCTGTGCGAAAGTCTACCTTTGATGCAGCCAGTT GGCTGC CD1A NM_001763 373GGAGTGGAAGGAACT 374 TCATGGGCGTATCTAG 375 CGCACCATTCGGTC 376GGAGTGGAAGGAACTGGAAACATTATTCCGTATACGCAC GGAAA AAT ATTTGAGGCATTCGGTCATTTGAGGGAATTCGTAGATACGCC CD276 NM_001024736 377CCAAAGGATGCGATA 378 GGATGACTTGGGAATC 379 CCACTGTGCAGCCT 380CCAAAGGATGCGATACACAGACCACTGTGCAGCCTTATT CACAG ATGTC TATTTCTCCAATGTCTCCAATGGACATGATTCCCAAGTCATCC CD44 NM_000610 381 GGCACCACTGCTT 382GATGCTCATGGTGAA 383 ACTGGAACCCAGAA 384GGCACCACTGCTTATGAAGGAAACTGGAACCCAGAA GCACA CD68 NM_001251 385TGGTTCCCAGCCC 386 CTCCTCCACCCTGGGT 387 CTCCAAGCCCAGAT 388TGGTTCCCAGCCCTGTGTCCACCTCCAAGCCCAGATT TCAGAT CD82 NM_002231 389GTGCAGGCTCAGGTG 390 GACCTCAGGGCGATTC 391 TCAGCTTCTACAAC 392GTGCAGGCTCAGGTGAAGTGCTGCGGCTGGGTCAGCTTC AAGTG ATGA TGGACAGACAACGCTACAACTGGACAGACAACGCTGAGCTCATGAAT TG CDC20 NM_001255 393 TGGATTGGAGTTC394 GCTTGCACTCCACAG 395 ACTGGCCGTGGCAC 396TGGATTGGAGTTCTGGGAATGTACTGGCCGTGGCAC TGGACA CDC25B NM_021873 397GCTGCAGGACCAG 398 TAGGGCAGCTGGCTT 399 CTGCTACCTCCCTT 400GCTGCAGGACCAGTGAGGGGCCTGCGCCAGTCCTGC GCCTTT CDC6 NM_001254 401GCAACACTCCCCA 402 TGAGGGGACCATTC 403 TTGTTCTCCACCAA 404GCAACACTCCCCATTTACCTCCTTGTTCTCCACCAAA AGCAAG CDH1 NM_004360 405TGAGTGTCCCCCGGT 406 CAGCCGCTTTCAGAT 407 TGCCAATCCCGATG 408TGAGTGTCCCCCGGTATCTTCCCCGCCCTGCCAATCCCG ATCTTC TTTCAT AAATTGGAAATTTATGAAATTGGAAATTTTATTGATGAAAATCTGAAA CDH10 NM_006727 409 TGTGGTGCAAGTC410 TGTAAATGACTCTGG 411 ATGCCGATGACCCT 412TGTGGTGCAAGTCACAGCTACAGATGCCGATGACCC TCATAT CDH11 NM_001797 413GTCGGCAGAAGCA 414 CTACTCATGGGCGGG 415 CCTTCTGCCCATAG 416GTCGGCAGAAGCAGGACTTGTACCTTCTGCCCATAG TGATCA CDH19 NM_021153 417AGTACCATAATGC 418 AGACTGCCTGTATAG 419 ACTCGGAAAACCAC 420AGTACCATAATGCGGGAACGCAAGACTCGGAAAACC AAGCG CDH5 NM_001795 421ACAGGAGACGTGT 422 CAGCAGTGAGGTGGT 423 TATTCTCCCGGTCC 424ACAGGAGACGTGTTCGCCATTGAGAGGCTGGACCGG AGCCTC CDH7 NM_033646 425GTTTGACATGGCT 426 AGTCACATCCCTCCG 427 ACCTCAACGTCATC 428GTTTGACATGGCTGCACTGAGAAACCTCAACGTCATC CGAGAC CDK14 NM_012395 429GCAAGGTAAATGG 430 GATAGCTGTGAAAGG 431 CTTCCTGCAGCCTG 432GCAAGGTAAATGGGAAGTTGGTAGCTCTGAAGGTGA ATCACC CDK2 NM_001798 433AATGCTGCACTACGA 434 TTGGTCACATCCTGG 435 CCTTGGCCGAAATC 436AATGCTGCACTACGACCCTAACAAGCGGATTTCGGCCAA CCCTA AAGAA CGCTTGTGGCAGCCCTGGCTCACCTTTCTTCCAGGATGTG CDK3 NM_001258 437 CCAGGAAGGGACT 438GTTGCATGAGCAGGT 439 CTCTGGCTCCAGAT 440CCAGGAAGGGACTGGAAGAGATTGTGCCCAATCTGG TGGGCA CDK7 NM_001799 441GTCTCGGGCAAAG 442 CTCTGGCCTTGTAAA 443 CCTCCCCAAGGAAG 444GTCTCGGGCAAAGCGTTATGAGAAGCTGGACTTCCT TCCAGC CDKN1A NM_000389 445TGGAGACTCTCAG 446 GGCGTTTGGAGTGGT 447 CGGCGGCAGACCAG 448TGGAGACTCTCAGGGTCGAAAACGGCGGCAGACCAG CATGA CDKN1C NM_000076 449CGGCGATCAAGAA 450 CAGGCGCTGATCTCT 451 CGGGCCTCTGATCT 452CGGCGATCAAGAAGCTGTCCGGGCCTCTGATCTCCG CCGATT CDKN2B NM_004936 453GACGCTGCAGAGC 454 GCGGGAATCTCTCCT 455 CACAGGATGCTGGC 456GACGCTGCAGAGCACCTTTGCACAGGATGCTGGCCT CTTTGC CDKN2C NM_001262 457GAGCACTGGGCAA 458 CAAAGGCGAACGGGA 459 CCTGTAACTTGAGG 460GAGCACTGGGCAATCGTTACGACCTGTAACTTGAGG GCCACC CDKN3 NM_005192 461TGGATCTCTACC 462 ATGTCAGGAGTCCCT 463 ATCACCCATCATCA 464TGGATCTCTACCAGCAATGTGGAATTATCACCCATCA TCCAAT CDS2 NM_003818 465GGGCTTCTTTGCT 466 ACAGGGCAGACAAAG 467 CCCGGACATCACAT 468GGGCTTCTTTGCTACTGTGGTGTTTGGCCTTCTGCTG AGGACA CENPF NM_016343 469CTCCCGTCAACAG 470 GGGTGAGTCTGGCCT 471 ACACTGGACCAGGA 472CTCCCGTCAACAGCGTTCTTTCCAAACACTGGACCAG GTGCAT CHAF1A NM_005483 473GAACTCAGTGTAT 474 GCTCTGTAGCACCTG 475 TGCACGTACCAGCA 476GAACTCAGTGTATGAGAAGCGGCCTGACTTCAGGAT CATCCT CHN1 NM_001822 477TTACGACGCTCGT 478 TCTCCCTGATGCACAT 479 CCACCATTGGCCGC 480TTACGACGCTCGTGAAAGCACATACCACTAAGCGGC TTAGTG CHRAC1 NM_017444 481TCTCGCTGCCTCTA 482 CCTGGTTGATGCTGG 483 ATCCGGGTCATCAT 484TCTCGCTGCCTCTATCCCGCATCCGGGTCATCATGAA GAAGAG CKS2 NM_001827 485GGCTGGACGTGGT 486 CGCTGCAGAAAATGA 487 CTGCGCCCGCTCTT 488GGCTGGACGTGGTTTTGTCTGCTGCGCCCGCTCTTCG CGCG CLDN3 NM_001306 489ACCAACTGCGTGC 490 GGCGAGAAGGAACAG 491 CAAGGCCAAGATCA 492ACCAACTGCGTGCAGGACGACACGGCCAAGGCCAAG CCATCG CLTC NM_004859 493ACCGTATGGACAG 494 TGACTACAGGATCAG 495 TCTCACATGCTGTA 496ACCGTATGGACAGCCACAGCCTGGCTTTGGGTACAG CCCAAA COL11A NM_001854 497GCCCAAGAGGGGA 498 GGACCTGGGTCTCCA 499 CTGCTCGACCTTTG 500GCCCAAGAGGGGAAGATGGCCCTGAAGGACCCAAAG GGTCCT COL1A1 NM_000088 501GTGGCCATCCAGC 502 CAGTGGTAGGTGATG 503 TCCTGCGCCTGATG 504GTGGCCATCCAGCTGACCTTCCTGCGCCTGATGTCCA TCCACC COL1A2 NM_000089 505CAGCCAAGAACTGGT 506 AAACTGGCTGCCAGCA 507 TCTCCTAGCCAGAC 508CAGCCAAGAACTGGTATAGGAGCTCCAAGGACAAGAAAC ATAGGAGCT TTG GTGTTTCTTGTCCTACGTCTGGCTAGGAGAAACTATCAATGCTGGCA TG COL3A1 NM_000090 509 GGAGGTTCTGGAC510 ACCAGGACTGCCACG 511 CTCCTGGTCCCCAA 512GGAGGTTCTGGACCTGCTGGTCCTCCTGGTCCCCAAG GGTGTC COL4A1 NM_001845 513ACAAAGGCCTCCC 514 GAGTCCCAGGAAGAC 515 CTCCTTTGACACCA 516ACAAAGGCCTCCCAGGATTGGATGGCATCCCTGGTG GGGATG COL5A1 NM_000093 517CTCCCTGGGAAAG 518 CTGGACCAGGAAGCC 519 CCAGGGAAACCACG 520CTCCCTGGGAAAGATGGCCCTCCAGGATTACGTGGT TAATCC COL5A2 NM_000393 521GGTCGAGGAACCC 522 GCCTGGAGGTCCAAC 523 CCAGGAAATCCTGT 524GGTCGAGGAACCCAAGGTCCGCCTGGTGCTACAGGA AGCACC COL6A1 NM_001848 525GGAGACCCTGGTG 526 TCTCCAGGGACACCA 527 CTTCTCTTCCCTGA 528GGAGACCCTGGTGAAGCTGGCCCGCAGGGTGATCAG TCACCC COL6A3 NM_004369 529GAGAGCAAGCGAG 530 AACAGGGAACTGGCC 531 CCTCTTTGACGGCT 532GAGAGCAAGCGAGACATTCTGTTCCTCTTTGACGGCT CAGCCA COL8A1 NM_001850 533TGGTGTTCCAGGG 534 CCCTGTAAACCCTGA 535 CCTAAGGGAGAGCC 536TGGTGTTCCAGGGCTTCTCGGACCTAAGGGAGAGCC AGGAA COL9A2 NM_001852 537GGGAACCATCCAG 538 ATTCCGGGTGGACAG 539 ACACAGGAAATCCG 540GGGAACCATCCAGGGTCTGGAAGGCAGTGCGGATTT CACTGC CRISP3 NM_006061 541TCCCTTATGAACA 542 AACCATTGGTGCATA 543 TGCCAGTTGCCCAG 544TCCCTTATGAACAAGGAGCACCTTGTGCCAGTTGCCC ATAACT CSF1 NM_000757 545TGCAGCGGCTGATTG 546 CAACTGTTCCTGGTC 547 TCAGATGGAGACCT 548TGCAGCGGCTGATTGACAGTCGATGGAGACCTCGTGCCA ACA TACAAACTCA CGTGCCAAATTACAAATTACATTTGAGTTTGTAGACCAGGAACAGTT CSK NM_004383 549 CCTGAACATGAAG 550CATCACGTCTCCGAA 551 TCCCGATGGTCTGC 552CCTGAACATGAAGGAGCTGAAGCTGCTGCAGACCAT AGCAGC CSRP1 NM_004078 553ACCCAAGACCCTG 554 GCAGGGGTGGAGTGA 555 CCACCCTTCTCCAG 556ACCCAAGACCCTGCCTCTTCCACTCCACCCTTCTCCA GGACCC CTGF NM_001901 557GAGTTCAAGTGCCCT 558 AGTTGTAATGGCAGGC 559 AACATCATGTTCTT 560GAGTTCAAGTGCCCTGACGGCGAGGTCATGAAGAAGAAC GACG ACAG CTTCATGACCTCGCATGATGTTCATCAAGACCTGTGCCTGCCATTACA CTHRC1 NM_138455 561 TGGCTCACTTCGG562 TCAGCTCCATTGAAT 563 CAACGCTGACAGCA 564TGGCTCACTTCGGCTAAAATGCAGAAATGCATGCTGT TGCATT CTNNA1 NM_001903 565CGTTCCGATCCTCTA 566 AGGTCCCTGTTGGCCT 567 ATGCCTACAGCACC 568CGTTCCGATCCTCTATACTGCATCCCAGGCATGCCTACA TACTGCAT TATAGG CTGATGTCGCAGCACCCTGATGTCGCAGCCTATAAGGCCAACAGG CTNNB1 NM_001904 569 GGCTCTTGTGCGTAC570 TCAGATGACGAAGAGC 571 AGGCTCAGTGATGT 572GGCTCTTGTGCGTACTGTCCTTCGGGCTGGTGACAGGGA TGTCCTT ACAGATG CTTCCCTGTCACCAAGACATCACTGAGCCTGCCATCTGTGCTCTTCGTC G CTNND1 NM_001331 573 CGGAAACTTCGGG574 CTGAATCCTTCTGCCC 575 TTGATGCCCTCATT 576CGGAAACTTCGGGAATGTGATGGTTTAGTTGATGCC TTCATT CTNND2 NM_001332 577GCCCGTCCCTACA 578 CTCACACCCAGGAGT 579 CTATGAAACGAGCC 580GCCCGTCCCTACAGTGAACTGAACTATGAAACGAGC ACTACC CTSB NM_001908 581GGCCGAGATCTAC 582 GCAGGAAGTCCGAAT 583 CCCCGTGGAGGGAG 584GGCCGAGATCTACAAAAACGGCCCCGTGGAGGGAGC CTTTCT CTSD BN_001909 585GTACATGATCCCCTG 586 GGGACAGCTTGTAGCC 587 ACCCTGCCCGCGAT 588GTACATGATCCCCTGTGAGAAGGTGTCCACCCTGCCCGC TGAGAAGGT TTTGC CACACTGAGATCACACTGAAGCTGGGAGGCAAAGGCTACAAG CTSK NM_000396 589 AGGCTTCTCTTGG 590CCACCTCTTCACTGGT 591 CCCCAGGTGGTTCA 592AGGCTTCTCTTGGTGTCCATACATATGAACTGGCTAT TAGCCA CTSL2 NM_001333 593TGTCTCACTGAGC 594 ACCATTGCAGCCCTG 595 CTTGAGGACGCGAA 596TGTCTCACTGAGCGAGCAGAATCTGGTGGACTGTTC CAGTCC CTSS NM_004079 597TGACAACGGCTTT 598 TCCATGGCTTTGTAG 599 TGATAACAAGGGCA 600TGACAACGGCTTTCCAGTACATCATTGATAACAAGG TCGACT CUL1 NM_003592 601ATGCCCTGGTAAT 602 GCGACCACAAGCCTT 603 CAGCCACAAAGCCA 604ATGCCCTGGTAATGTCTGCATTCAACAATGACGCTGG GCGTCA CXCL12 NM_000609 605GAGCTACAGATGC 606 TTTGAGATGCTTGAC 607 TTCTTCGAAAGCCA 608GAGCTACAGATGCCCATGCCGATTCTTCGAAAGCCA TGTTGC CXCR4 NM_003467 609TGACCGCTTCTAC 610 AGGATAAGGCCAACC 611 CTGAAACTGGAACA 612TGACCGCTTCTACCCCAATGACTTGTGGGTGGTTGTG CAACCA CXCR7 NM_020311 613CGCCTCAGAACGATG 614 GTTGCATGGCCAGCTG 615 CTCAGAGCCAGGGA 616CGCCTCAGAACGATGGATCTGCATCTTCGACTACTCAGA GAT AT ACTTCTCGGAGCCAGGGAACTTCTCGGACATCAGCTGGCCAT CYP3A5 NM_000777 617 TCATTGCCCAGTA 618GACAGGCTTGCCTTT 619 TCCCGCCTCAAGTT 620TCATTGCCCAGTATGGAGATGTATTGGTGAGAAACTT TCTCAC CYR61 NM_001554 621TGCTCATTCTTGAG 622 GTGGCTGCATTAGTG 623 CAGCACCCTTGGCA 624TGCTCATTCTTGAGGAGCATTAAGGTATTTCGAAACT GTTTCG DAG1 NM_004393 625GTGACTGGGCTCA 626 ATCCCACTTGTGCTCC 627 CAAGTCAGAGTTTC 628GTGACTGGGCTCATGCCTCCAAGTCAGAGTTTCCCTG CCTGGT DAP NM_004394 629CCAGCCTTTCTGG 630 GACCAGGTCTGCCTC 631 CTCACCAGCTGGCA 632CCAGCCTTTCTGGTGCTGTTCTCCAGTTCACGTCTGC GACGTG DAPK1 NM_004938 633CGCTGACATCATG 634 TCTCTTTCAGCAACGA 635 TCATATCCAAACTC 636CGCTGACATCATGAATGTTCCTCGACCGGCTGGAGG GCCTCC DARC NM_002036 637GCCCTCATTAGTC 638 CAGACAGAAGGGCTG 639 TCAGCGCCTGTGCT 640GCCCTCATTAGTCCTTGGCTCTTATCTTGGAAGCACA TCCAAG DDIT4 NM_019058 641CCTGGCGTCTGTC 642 CGAAGAGGAGGTGGA 643 CTAGCCTTTGGGAC 644CCTGGCGTCTGTCCTCACCATGCCTAGCCTTTGGGAC CGCTTC DDR2 NM_001014796 645CTATTACCGGATCCA 646 CCCAGCAAGATACTCT 647 AGTGCTCCCTATCC 648CTATTACCGGATCCAGGGCCGGGCAGTGCTCCCTATCCG GGGC CCCA GCTGGATGTCCTGGATGTCTTGGGAGAGTATCTTGCTGGG DES NM_001927 649 ACTTCTCACTGGC 650GCTCCACCTTCTCGTT 651 TGAACCAGGAGTTT 652ACTTCTCACTGGCCGACGCGGTGAACCAGGAGTTTCT CTGACC DHRS9 NM_005771 653GGAGAAAGGTCTC 654 CAGTCAGTGGGAGCC 655 ATCAATAATGCTGG 656GGAGAAAGGTCTCTGGGGTCTGATCAATAATGCTGG TGTTCC DHX9 NM_001357 657GTTCGAACCATCT 658 TCCAGTTGGATTGTG 659 CCAAGGAACCACAC 660GTTCGAACCATCTCAGCGACAAAACCAAGTGGGTGT CCACTT DIAPH1 NM_005219 661CAAGCAGTCAAGG 662 AGTTTTGCTCGCCTCA 663 TTCTTCTGTCTCCC 664CAAGCAGTCAAGGAGAACCAGAAGCGGCGGGAGAC GCCGCT DICER1 NM_177438 665TCCAATTCCAGCA 666 GGCAGTGAAGGCGAT 667 AGAAAAGCTGTTTG 668TCCAATTCCAGCATCACTGTGGAGAAAAGCTGTTTGT TCTCCC DIO2 NM_013989 669CTCCTTTCACGAG 670 AGGAAGTCAGCCACT 671 ACTCTTCCACCAGT 672CTCCTTTCACGAGCCAGCTGCCAGCCTTCCGCAAACT TTGCGG DLC1 NM_006094 673GATTCAGACGAGG 674 CACCTCTTGCTGTCCC 675 AAAGTCCATTTGCC 676GATTCAGACGAGGATGAGCCTTGTGCCATCAGTGGC ACTGAT DLGAP1 NM_004746 677CTGCTGAGCCCAG 678 AGCCTGGAAGGAGTT 679 CGCAGACCACCCAT 680CTGCTGAGCCCAGTGGAGCACCACCCCGCAGACCAC ACTACA DLL4 NM_019074 681CACGGAGGTATAA 682 AGAAGGAAGGTCCAG 683 CTACCTGGACATCC 684CACGGAGGTATAAGGCAGGAGCCTACCTGGACATCC CTGCTC DNM3 NM_015569 685CTTTCCCACCCGG 686 AAGGACCTTCTGCAG 687 CATATCGCTGACCG 688CTTTCCCACCCGGCTTACAGACATATCGCTGACCGAA AATGGG DPP4 NM_001935 689GTCCTGGGATCGG 690 GTACTCCCACCGGGA 691 CGGCTATTCCACAC 692GTCCTGGGATCGGGAAGTGGCGTGTTCAAGTGTGGA TTGAAC DPT NM_001937 693CACCTAGAAGCCT 694 CAGTAGCTCCCCAGG 695 TTCCTAGGAAGGCT 696CACCTAGAAGCCTGCCCACGATTCCTAGGAAGGCTG GGCAGA DUSP1 NM_004417 697AGACATCAGCTCC 698 GACAAACACCCTTCC 699 CGAGGCCATTGACT 700AGACATCAGCTCCTGGTTCAACGAGGCCATTGACTTC TCATAG DUSP6 NM_001946 701CATGCAGGGACTG 702 TGCTCCTACCCTATCA 703 TCTACCCTATGCGC 704CATGCAGGGACTGGGATTCGAGGACTTCCAGGCGCA CTGGAA DVL1 NM_004421 705TCTGTCCCACCTG 706 TCAGACTGTTGCCGG 707 CTTGGAGCAGCCTG 708TCTGTCCCACCTGCTGCTGCCCCTTGGAGCAGCCTGC CACCTT DYNLL1 NM_001037494 709GCCGCCTACCTCACA 710 GCCTGACTCCAGCTCT 711 ACCCACGTCAGTGA 712GCCGCCTACCTCACAGACTTGTGAGCACTCACTGACGTG GAC CCT GTGCTCACAAGGTAGCGCCCAGGGCCTGCGGGGCGCAGGAGAG EBNA1BP2 NM_006824 713 TGCGGCGAGATGGAC714 GTGACAAGGGATTCAT 715 CCCGCTCTCGGATT 716TGCGGCGAGATGGACACTCCCCCGCTCTCGGATTCGGAG ACT CGGATT CGGAGTCGTCGGAATCCGATGAATCCCTTGTCAC ECE1 NM_001397 717 ACCTTGGGATCTG 718GGACCAGGACCTCCA 719 TCCACTCTCGATAC 720ACCTTGGGATCTGCCTCCAAGCTGGTGCAGGGTATC CCTGCA EDN1 NM_001955 721TGCCACCTGGACA 722 TGGACCTAGGGCTTC 723 CACTCCCGAGCACG 724TGCCACCTGGACATCATTTGGGTCAACACTCCCGAGC TTGTTC EDNRA NM_001957 725TTTCCTCAAATTTG 726 TTACACATCCAACCA 727 CCTTTGCCTCAGGG 728TTTCCTCAAATTTGCCTCAAGATGGAAACCCTTTGCC CATCCT EFNB2 NM_004093 729TGACATTATCATCCC 730 GTAGTCCCCGCTGACC 731 CGGACAGCGTCTTC 732TGACATTATCATCCCGCTAAGGACTGCGGACAGCGTCTT GCTAAGGA TTCTC TGCCCTCACTCTGCCCTCACTACGAGAAGGTCAGCGGGGACTA EGF NM_001963 733 CTTTGCCTTGCTCTG 734AAATACCTGACACCCT 735 AGAGTTTAACAGCC 736CTTTGCCTTGCTCTGTCACAGTGAAGTCAGCCAGAGCAG TCACAGT TATGACAAATTCTGCTCTGGCTGAC GGCTGTTAAACTCTGTGAAATTTGTCATAAGGGTG TT EGR1 NM_001964 737GTCCCCGCTGCAGAT 738 CTCCAGCTTAGGGTAG 739 CGGATCCTTTCCTC 740GTCCCCGCTGCAGATCTCTGACCCGTTCGGATCCTTTCC CTCT TTGTCCAT ACTCGCCCATACTCGCCCACCATGGACAACTACCCTAAGCTGG EGR3 NM_004430 741 CCATGTGGATGAATG742 TGCCTGAGAAGAGGTG 743 ACCCAGTCTCACCT 744CCATGTGGATGAATGAGGTGTCTCCTTTCCATACCCAGT AGGTG AGGT TCTCCCCACCCTCACCTTCTCCCCACCCTACCTCACCTCTTCTCA EIF2C2 NM_012154 745 GCACTGTGGGCAG746 ATGTTTGGTGACTGG 747 CGGGTCACATTGCA 748GCACTGTGGGCAGATGAAGAGGAAGTACCGCGTCTG GACACG EIF2S3 NM_001415 749CTGCCTCCCTGATT 750 GGTGGCAAGTGCCTG 751 TCTCGTGCTTCAGC 752CTGCCTCCCTGATTCAAGTGATTCTCGTGCTTCAGCC CTCCCA EIF3H NM_003756 753CTCATTGCAGGCCAG 754 GCCATGAAGAGCTTGC 755 CAGAACATCAAGGA 756CTCATTGCAGGCCAGATAAACACTTACTGCCAGAACATC ATAAA CTA GTTCACTGCCCAAAGGAGTTCACTGCCCAAAACTTAGGCAAGCTC EIF4E NM_001968 757 GATCTAAGATGGCGA758 TTAGATTCCGTTTTCT 759 ACCACCCCTACTCC 760GATCTAAGATGGCGACTGTCGAACCGGAAACCACCCCTA CTGTCGAA CCTCTTCTG TAATCCCCCGACTCTCCTAATCCCCCGACTACAGAAGAGGAGAAAA EIF5 NM_001969 761 GAATTGGTCTCCA 762TCCAGGTATATGGCT 763 CCACTTGCACCCGA 764GAATTGGTCTCCAGCTGCCTTTGATCAAGATTCGGGT ATCTTG ELK4 NM_001973 765GATGTGGAGAATG 766 AGTCATTGCGGCTAG 767 ATAAACCACCTCAG 768GATGTGGAGAATGGAGGGAAAGATAAACCACCTCAG CCTGGT ENPP2 NM_006209 769CTCCTGCGCACTA 770 TCCCTGGATAATTGG 771 TAACTTCCTCTGGC 772CTCCTGCGCACTAATACCTTCAGGCCAACCATGCCAG ATGGTT ENY2 NM_020189 773CCTCAAAGAGTTG 774 CCTCTTTACAGTGTGC 775 CTGATCCTTCCAGC 776CCTCAAAGAGTTGCTGAGAGCTAAATTAATTGAATGT CACATT EPHA2 NM_004431 777CGCCTGTTCACCA 778 GTGGCGTGCCTCGAA 779 TGCGCCCGATGAGA 780CGCCTGTTCACCAAGATTGACACCATTGCGCCCGATG TCACCG EPHA3 NM_005233 781CAGTAGCCTCAAG 782 TTCGTCCCATATCCAG 783 TATTCCAAATCCGA 784CAGTAGCCTCAAGCCTGACACTATATACGTATTCCAA GCCCGA EPHB2 NM_004442 785CAACCAGGCAGCT 786 GTAATGCTGTCCACG 787 CACCTGATGCATGA 788CAACCAGGCAGCTCCATCGGCAGTGTCCATCATGCA TGGACA EPHB4 NM_004444 789TGAACGGGGTATCCT 790 AGGTACCTCTCGGTCA 791 CGTCCCATTTGAGC 792TGAACGGGGTATCCTCCTTAGCCAGGGGCCCGTCCCATT CCTTA GTGG CTGTCAATGTTGAGCCTGTCAATGTCACCACTGACCGAGAGGT ERBB2 NM_004448 793 CGGTGTGAGAAGT 794CCTCTCGCAAGTGCT 795 CCAGACCATAGCAC 796CGGTGTGAGAAGTGCAGCAAGCCCTGTGCCCGAGTG ACTCGG ERBB3 NM_001982 797CGGTTATGTCATGCC 798 GAACTGAGACCCACTG 799 CCTCAAAGGTACTC 800CGGTTATGTCATGCCAGATACACACCTCAAAGGTACTCC AGATACAC AAGAAAGG CCTCCTCCCGGCTCCTCCCGGGAAGGCACCCTTTCTTCAGTGGGTC ERBB4 NM_005235 801 TGGCTCTTAATCAGT802 CAAGGCATATCGATCC 803 TGTCCCACGAATAA 804TGGCTCTTAATCAGTTTCGTTACCTGCCTCTGGAGAATT TTCGTTACCT TCATAAAGTTGCGTAAATTCTCC TACGCATTATTCGTGGGACAAAACTTTATGAGGAT AG ERCC1 NM_001983805 GTCCAGGTGGATG 806 CGGCCAGGATACACA 807 CAGCAGGCCCTCAA 808GTCCAGGTGGATGTGAAAGATCCCCAGCAGGCCCTC GGAGCT EREG NM_001432 809TGCTAGGGTAAAC 810 TGGAGACAAGTCCTG 811 TAAGCCATGGCTGA 812TGCTAGGGTAAACGAAGGCATAATAAGCCATGGCTG CCTCTG ERG NM_004449 813CCAACACTAGGCT 814 CCTCCGCCAGGTCTTT 815 AGCCATATGCCTTC 816CCAACACTAGGCTCCCCACCAGCCATATGCCTTCTCA TCATCT ESR1 NM_000125 817CGTGGTGCCCCTC 818 GGCTAGTGGGCGCAT 819 CTGGAGATGCTGGA 820CGTGGTGCCCCTCTATGACCTGCTGCTGGAGATGCTG CGCCC ESR2 NM_001437 821TGGTCCATCGCCAGT 822 TGTTCTAGCGATCTTG 823 ATCTGTATGCGGAA 824TGGTCCATCGCCAGTTATCACATCTGTATGCGGAACCTC TATCA CTTCACA CCTCAAAAGAGTCCAAAAGAGTCCCTGGTGTGAAGCAAGATCGCTAGA CT ETV1 NM_004956 825 TCAAACAAGAGCC826 AACTGCCAGAGCTGA 827 ATCGGGAAGGACCC 828TCAAACAAGAGCCAGGAATGTATCGGGAAGGACCCA ACATAC ETV4 NM_001986 829TCCAGTGCCTATG 830 ACTGTCCAAGGGCAC 831 CAGACAAATCGCCA 832TCCAGTGCCTATGACCCCCCCAGACAAATCGCCATCA TCAAGT EZH2 NM_004456 833TGGAAACAGCGAAGG 834 CACCGAACACTCCCTA 835 TCCTGACTTCTGTG 836TGGAAACAGCGAAGGATACAGCCTGTGCACATCCTGACT ATACA GTCC AGCTCATTGCGTCTGTGAGCTCATTGCGCGGGACTAGGGAGTGTT F2R NM_001992 837 AAGGAGCAAACCA 838GCAGGGTTTCATTGA 839 CCCGGGCTCAACAT 840AAGGAGCAAACCATCCAGGTGCCCGGGCTCAACATC CACTAC FAAH NM_001441 841GACAGCGTAGTGGTG 842 AGCTGAACATGGACTG 843 TGCCCTTCGTGCAC 844GACAGCGTGGTGGTGCATGTGCTGAAGCTGCAGGGTGCC CATGT TGGA ACCAATGGTGCCCTTCGTGCACACCAATGTTCCACAGTCCA FABP5 NM_001444 845 GCTGATGGCGAGAAA846 CTTTCCTTCCCATCCC 847 CCTGATGCTGAACC 848GCTGATGGCAGAAAAACTCAGACTGTCTGCAACTTTACA AACTCA ACT AATGCACCATGATGGTGCATTGGTTCAGCATCAGGAGTGGGAT FADD NM_003824 849 GTTTTCGCGAGAT 850CTCCGGTGCCTGATTC 851 AACGCGCTCTTGTC 852GTTTTCGCGAGATAACGGTCGAAAACGCGCTCTTGTC GATTTC FAM107 NM_007177 853AAGTCAGGGAAAA 854 GCTGGCCCTACAGCT 855 AATTGCCACACTGA 856AAGTCAGGGAAAACCTGCGGAGAATTGCCACACTGA CCAGCG FAM13C NM_198215 857ATCTTCAAAGCGG 858 GCTGGATACCACATG 859 TCCTGACTTTCTCC 860ATCTTCAAAGCGGAGAGCGGGAGGAGCCACGGAGAA GTGGCT FAM171B NM_177454 861CCAGGAAGGAAAAGC 862 GTGGTCTGCCCCTTCT 863 TGAAGATTTTGAAG 864CCAGGAAGGAAAAGCACTGTTGAAGATTTTGAAGCTAAT ACTGT TTTA CTAATACATCCCCCACATCCCCCACTAAAAGAAGGGGCAGACCAC AC FAM49B NM_016623 865 AGATGCAGAAGGC866 GCTGGATTGCCTCTC 867 TGGCCAGCTCCTCT 868AGATGCAGAAGGCATCTTGGAGGACTTGCAGTCATA GTATGA FAM73A NM_198549 869TGAGAAGGTGCGCTA 870 GGCCATTAAAAGCTCA 871 AAGACCTCATGCAG 872TGAGAAGGTGCGCTATTCAAGTACAGAGACTTTAGCTGA TTCAA GTGC TTACTCATTCGCCAGACCTCATGCAGTTACTCATTCGCCGCACTGAG FAP NM_004460 873 GTTGGCTCACGTG 874GACAGGACCGAAACA 875 AGCCACTGCAAACA 876GTTGGCTCACGTGGGTTACTGATGAACGAGTATGTTT TACTCG FAS NM_000043 877GGATTGCTCAACAAC 878 GGCATTAACACTTTTG 879 TCTGGACCCTCCTA 880GGATTGCTCAACAACCATGCTGGGCATCTGGACCCTCCT CATGCT GACGATAA CCTCTGGTTCTTACACCTCTGGTTCTTACGTCTGTTGCTAGATTATCG GT FASLG NM_000639 881GCACTTTGGGATTCT 882 GCATGTAAGAAGACCC 883 ACAACATTCTCGGT 884GCACTTTGGGATTCTTTCCATTATGATTCTTTGTTACAG TTCCATTAT TCACTGAAGCCTGTAACAAAGA GCACCGAGAATGTTGTATTCAGTGAGGGTCTTCTT A FASN NM_004104 885GCCTCTTCCTGTTC 886 GCTTTGCCCGGTAGC 887 TCGCCCACCTACGT 888GCCTCTTCCTGTTCGACGGCTCGCCCACCTACGTACT ACTGGC FCGR3A NM_000569 889GTCTCCAGTGGAA 890 AGGAATGCAGCTACT 891 CCCATGATCTTCAA 892GTCTCCAGTGGAAGGGAAAAGCCCATGATCTTCAAG GCAGGG FGF10 NM_004465 893TCTTCCGTCCCTGT 894 AGAGTTGGTGGCCTC 895 ACACCATGTCCTGA 896TCTTCCGTCCCTGTCACCTGCCAAGCCCTTGGTCAGG CCAAGG FGF17 NM_003867 897GGTGGCTGTCCTC 898 TCTAGCCAGGAGGAG 899 TTCTCGGATCTCCC 900GGTGGCTGTCCTCAAAATCTGCTTCTCGGATCTCCCT TCAGTC FGF5 NM_004464 901GCATCGGTTTCCA 902 AACATATTGGCTTCGT 903 CCATTGACTTTGCC 904GCATCGGTTTCCATCTGCAGATCTACCCGGATGGCAA ATCCGG FGF6 NM_020996 905GGGCCATTAATTCTG 906 CCCGGGACATAGTGAT 907 CATCCACCTTGCCT 908GGGCCATTAATTCTGACCACGTGCCTGAGAGGCAAGGTG ACCAC GAA CTCAGGCACGATGGCCCTGGGACAGAAACTGTTCATCATCTAT FGF7 NM_002009 909 CCAGAGCAAATGGCT910 TCCCCTCCTTCCATGT 911 CAGCCCTGAGCGAC 912CCAGAGCAAATGGCTACAAATGTGAACTGTTCCAGCCCT ACAAA AATC ACACAAGAAGGAGCGACACACAAGAAGTTATGATTACATGGAA FGFR2 NM_000141 913 GAGGGACTGTTGGCA914 GAGTGAGAATTCGATC 915 TCCCAGAGACCAAC 916GAGGGACTGTTGGCATGCAGTGCCCTCCCAGAGACCAAC TGCA CAAGTCTTC GTTCAAGCAGTTGGTTCAAGCAGTTGGTAGAAGACTTGGATCGAAT FGFR4 NM_002011 917 CTGGCTTAAGGATGG918 ACGAGACTCCAGTGCT 919 CCTTTCATGGGGAG 920CTGGCTTAAGGATGGACAGGCCTTTCATGGGGAGAACCG ACAGG GATG AACCGCATTCATTGGAGGCATTCGGCTGCGCCATCAGCACTG FKBP5 NM_004117 921 CCCACAGTAGAGG 922GGTTCTGGCTTTCACG 923 TCTCCCCAGTTCCA 924CCCACAGTAGAGGGGTCTCATGTCTCCCCAGTTCCAC CAGCAG FLNA NM_001456 925GAACCTGCGGTGG 926 GAAGACACCCTGGCC 927 TACCAGGCCCATAG 928GAACCTGCGGTGGACACTTCCGGTGTCCAGTGCTAT CACTGG FLNC NM_001458 929CAGGACAATGGTG 930 TGATGGTGTACTCGC 931 ATGTGCTGTCAGCT 932CAGGACAATGGTGATGGCTCATGTGCTGTCAGCTAC ACCTGC FLT1 NM_002019 933GGCTCCTGAATCT 934 TCCCACAGCAATACT 935 CTACAGCACCAAGA 936GGCTCCTGAATCTATCTTTGACAAAATCTACAGCACC GCGAC FLT4 NM_002020 937ACCAAGAAGCTGA 938 CCTGGAAGCTGTAGC 939 AGCCCGCTGACCAT 940ACCAAGAAGCTGAGGACCTGTGGCTGAGCCCGCTGA GGAAGA FN1 NM_002026 941GGAAGTGACAGAC 942 ACACGGTAGCCGGTC 943 ACTCTCAGGCGGTG 944GGAAGTGACAGACGTGAAGGTCACCATCATGTGGAC TCCACA FOS NM_005252 945CGAGCCCTTTGATGA 946 GGAGCGGGCTGTCTCA 947 TCCCAGCATCATCC 948CGAGCCCTTTGATGACTTCCTGTTCCCAGCATCATCCAG CTTCCT GA AGGCCCAGGCCCAGTGGCTCTGAGACAGCCCGCTCC FOXO1 NM_002015 949 GTAAGCACCATGC 950GGGGCAGAGGCACTT 951 TATGAACCGCCTGA 952GTAAGCACCATGCCCCACACCTCGGGTATGAACCGC CCCAAG FOXP3 NM_014009 953CTGTTTGCTGTCCG 954 GTGGAGGAACTCTGG 955 TGTTTCCATGGCTA 956CTGTTTGCTGTCCGGAGGCACCTGTGGGGTAGCCAT CCCCAC FOXQ1 NM_033260 957TGTTTTTGTCGCAA 958 TGGAAAGGTTCCCTG 959 TGATTTATGTCCCT 960TGTTTTTGTCGCAACTTCCATTGATTTATGTCCCTTCC TCCCTC FSD1 NM_024333 961AGGCCTCCTGTCC 962 TGTGTGAACCTGGTC 963 CGCACCAAACAAGT 964AGGCCTCCTGTCCTTCTACAATGCCCGCACCAAACAA GCTGCA FYN NM_002037 965GAAGCGCAGATCA 966 CTCCTCAGACACCAC 967 CTGAAGCACGACAA 968GAAGCGCAGATCATGAAGAAGCTGAAGCACGACAAG GCTGGT G6PD NM_000402 969AATCTGCCTGTGG 970 CGAGATGTTGCTGGT 971 CCAGCCTCAGTGCC 972AATCTGCCTGTGGCCTTGCCCGCCAGCCTCAGTGCCA ACTTGA GABRG2 NM_198904 973CCACTGTCCTGACAA 974 GAGATCCATCGCTGTG 975 CTCAGCACCATTGC 976CCACTGTCCTGACAATGACCACCCTCAGCACCATTGCCC TGACC ACAT CCGGAAATGGAAATCGCTCCCCAAGGTCTCCTATGTCAGAGC GADD45 NM_001924 977 GTGCTGGTGACGA978 CCCGGCAAAAACAAA 979 TTCATCTCAATGGA 980GTGCTGGTGACGAATCCACATTCATCTCAATGGAAG AGGATC GADD45 NM_015675 981ACCCTCGACAAGA 982 TGGGAGTTCATGGGT 983 TGGGAGTTCATGGG 984ACCCTCGACAAGACCACACTTTGGGACTTGGGAGCT TACAGA GDF15 NM_004864 985CGCTCCAGACCTA 986 ACAGTGGAAGGACCA 987 TGTTAGCCAAAGAC 988CGCTCCAGACCTATGATGACTTGTTAGCCAAAGACTG TGCCAC GHR NM_000163 989CCACCTCCCACAG 990 GGTGCGTGCCTGTAG 991 CGTGCCTCAGCCTC 992CCACCTCCCACAGGTTCAGGCGATTCCCGTGCCTCAG CTGAGT GNPTAB NM_024312 993GGATTCACATCGC 994 GTTCTTGCATAACAAT 995 CCCTGCTCACATGC 996GGATTCACATCGCGGAAAGTCCCTGCTCACATGCCTC CTCACA GNRH1 NM_000825 997AAGGGCTAAATCCAG 998 CTGGATCTCTGTGGCT 999 TCCTGTCCTTCACT 1000AAGGGCTAAATCCAGGTGTGACGGTATCTAATGATGTCC GTGTG GGT GTCCTTGCCATGTCCTTCACTGTCCTTGCCATCACCAGCCACAG GPM6B NM_001001094 1001ATGTGCTTGGAGTGG 1002 TGTAGAACATAAACAC 1003 CGCTGAGAAACCAA 1004ATGTGCTTGGAGTGGCCTGGCTGGGTGTGTTTGGTTTCT CCT GGGCA ACACACCCAGCAGCGGTGCCCGTGTTTATGTTCTACA GPNMB NM_001005340 1005 CAGCCTCGCCTTTAA 1006TGACAAATATGGCCAA 1007 CAAACAGTGCCCTG 1008CAGCCTCGCCTTTAAGGATGGCAAACAGTGCCCTGATCT GGAT GCAG ATCTCCGTTGCCGTTGGCTGCTTGGCCATATTTGTCA GPR68 NM_003485 1009 CAAGGACCAGATC 1010GGTAGGGCAGGAAGC 1011 CTCAGCACCGTGGT 1012CAAGGACCAGATCCAGCGGCTGGTGCTCAGCACCGT CATCTT GPS1 NM_004127 1013AGTACAAGCAGGC 1014 GCAGCTCAGGGAAGT 1015 CCTCCTGCTGGCTT 1016AGTACAAGCAGGCTGCCAAGTGCCTCCTGCTGGCTT CCTTTG GRB7 NM_005310 1017CCATCTGCATCCA 1018 GGCCACCAGGGTATT 1019 CTCCCCACCCTTGA 1020CCATCTGCATCCATCTTGTTTGGGTCCCCACCCTTG GAAGTG GREM1 NM_013372 1021GTGTGGGCAAGGA 1022 GACCTGATTTGGCCT 1023 TCCACCCTCCCTTT 1024GTGTGGGCAAGGACAAGCAGGATAGTGGAGTGAGAA CTCACT GSK3B NM_002093 1025GACAAGGACGGCA 1026 TTGTGGCCTGTCTGG 1027 CCAGGAGTTGCCAC 1028GACAAGGACGGCAGCAAGGTGACAACAGTGGTGGCA CACTGT GSN NM_000177 1029CTTCTGCTAAGCGGT 1030 GGCTCAAAGCCTTGCT 1031 ACCCAGCCAATCGG 1032CTTCTGCTAAGCGGTACATCGAGACGGACCCAGCCAATC ACATCGA TCAC GATCGGCGGGATCGGCGGACGCCCATACCGTGGTGAAGC GSTM1 NM_000561 1033 AAGCTATGAGGAAAA1034 GGCCCAGCTTGAATTT 1035 TCAGCCACTGGCTT 1036AAGCTATGAGGAAAAGAAGTACACGATGGGGGACGCTCC GAAGTACACGA TTCA CTGTCATAATCAGGTGATTATGACAGAAGCCAGTGGCTGAATGAAAA AG GSTM2 NM_000848 1037 CTGCAGGCACTCC1038 CCAAGAAACCATGGC 1039 CTGAAGCTCTACTC 1040CTGCAGGCACTCCCTGAAATGCTGAAGCTCTACTCAC ACAGTT HDAC1 NM_004964 1041CAAGTACCACAGCGA 1042 GCTTGCTGTACTCCG 1043 TTCTTGCGCTCCAT 1044CAAGTACCACAGCGATGACTACATTAAATTCTTGCGCTC TGACTACATTA ACATGTT CCGTCCAGACATCCGTCCAGATAACATGTCGGAGTACAGCAAG HDAC9 NM_178423 1045 AACCAGGCAGTCACC1046 CTCTGTCTTCCTGCA 1047 CCCCCTGAAGCTCT 1048AACCAGGCAGTCACCTTGAGGAAGCAGAGGAAGAGCTTC TTGAG TCGC TCCTCTGCTTAGGGGGACCAGGCGATGCAGGAAGACAGAG HGD NM_000187 1049 CTCAGGTCTGCCC 1050TTATTGGTGCTCCGT 1051 CTGAGCAGCTCTCA 1052CTCAGGTCTGCCCCTACAATCTCTATGCTGAGCAGCT G GGATCG HIP1 NM_005338 1053CTCAGAGCCCCAC 1054 GGGTTTCCCTGCCAT 1055 CGACTCACTGACCG 1056CTCAGAGCCCCACCTGAGCCTGCCGACTCACTGACC AGGCCT HIRIP3 NM_003609 1057GGATGAGGAAAAG 1058 TCCCTAGCTGACTTTC 1059 CCATTGCTCCTGGT 1060GGATGAGGAAAAGGGGGATTGGAAACCCAGAACCAG TCTGGG HK1 NM_000188 1061TACGCACAGAGGC 1062 GAGAGAAGTGCTGGA 1063 TAAGAGTCCGGGAT 1064TACGCACAGAGGCAAGCAGCTAAGAGTCCGGGATCC CCCCAG HLA-G NM_002127 1065CCATCCCCATCAT 1066 CCGCAGCTCCAGTGA 1067 CTGCAAGGACAACC 1068CCTGCGCGGCTACTACAACCAGAGCGAGGCCAGTTC AGGCC HLF NM_002126 1069CACCCTGCAGGTG 1070 GGTACCTAGGAGCAG 1071 TAAGTGATCTGCCC 1072CACCCTGCAGGTGTCTGAGACTAAGTGATCTGCCCTC TCCAGG HNF1B NM_000458 1073TCCCAGCATCTCA 1074 CGTACCAGGTGTACA 1075 CCCCTATGAAGACC 1076TCCCAGCATCTCAACAAGGGCACCCCTATGAAGACC CAGAAG HPS1 NM_000195 1077GCGGAAGCTGTAT 1078 TTCGGATAAGATGAC 1079 CAGTCACCAGCCCA 1080GCGGAAGCTGTATGTGCTCAAGTACCTGTTTGAAGT AAGTGC HRAS NM_005343 1081GGACGAATACGAC 1082 GCACGTCTCCCCATC 1083 ACCACCTGCTTCCG 1084GGACGAATACGACCCCACTATAGAGGATTCCTACCG GTAGGA HSD17B10 NM_004493 1085CCAGCGAGTTCTTGA 1086 ATCTCACCAGCCACCA 1087 TCATGGGCACCTTC 1088CCACCAGACAAGACCGATTCGCTGGCCTCCATTTCTTCA TGTGA GG AATGTGATCCACCCAGTGCCTGTCATGAAACTTGTGG HSD17B2 NM_002153 1089 GCTTTCCAAGTGG 1090TGCCTGCGATATTTGT 1091 AGTTGCTTCCATCC 1092GCTTTCCAAGTGGGGAATTAAAGTTGCTTCCATCCAA AACCTG HSD17B3 NM_000197 1093GGGACGTCCTGGAAC 1094 TGGAGAATCTCACGCA 1095 CTTCATCCTCACAG 1096GGGACGTCCTGGAACAGTTCTTCATCCTCACAGGGCTGC AGT CTTC GGCTGCTGGTTGGTGTGCCTGGCCTGCCTGGCGAAGTGCGTGAG HSD17B4 NM_000414 1097 CGGGAAGCTTCAG1098 ACCTCAGGCCCAATA 1099 AGGCGGCGTCCTAT 1100CGGGAAGCTTCAGAGTACCTTTGTATTTGAGGAAAT TTCCTC HSD3B2 NM_000198 1101GCCTTCCTTTAACC 1102 GGAGTAAATTGGGCT 1103 ACTTCCAGCAGGAA 1104GCCTTCCTTTAACCCTGATGTACTGGATTGGCTTCCT GCCAAT HSP90AB1 NM_007355 1105GCATTGTGACCAGCA 1106 GAAGTGCCTGGGCTTT 1107 ATCCGCTCCATATT 1108GCATTGTGACCAGCACCTACGGCTGGACAGCCAATATGG CCTAC CAT GGCTGTCCAGAGCGGATCATGAAAGCCCAGGCACTTC HSPA5 NM_005347 1109 GGCTAGTAGAACTGG 1110GGTCTGCCCAAATGCT 1111 TAATTAGACCTAGG 1112GGCTAGTAGAACTGGATCCCAACACCAAACTCTTAATTA ATCCCAACA TTTC CCTCAGCTGCACTGGACCTAGGCCTCAGCTGCACTGCCCGAAAAGCA C HSPA8 NM_006597 1113 CCTCCCTCTGGTGGT1114 GCTACATCTACACTTG 1115 CTCAGGGCCCACCA 1116CCTCCCTCTGGTGGTGCTTCCTCAGGGCCCACCATTGAA GCTT GTTGGCTTAA TTGAAGAGGTTGGAGGTTGATTAAGCCAACCAAGTGTAGATGTAGC HSPB1 NM_001540 1117 CCGACTGGAGGAGCA1118 ATGCTGGCTGACTCTG 1119 CGCACTTTTCTGAG 1120CCGACTGGAGGAGCATAAAAGCGCAGCCGAGCCCAGCGC TAAA CTC CAGACGTCCACCCGCACTTTTCTGAGCAGACGTCCAGAGCAGA HSPB2 NM_001541 1121 CACCACTCCAGAG1122 TGGGACCAAACCATA 1123 CACCTTTCCCTTCC 1124CACCACTCCAGAGGTAGCAGCATCCTTGGGGGAAGG CCCAAG HSPE1 NM_002157 1125GCAAGCAACAGTAGT 1126 CCAACTTTCACGCTAA 1127 TCTCCACCCTTTCC 1128GCAAGCAACAGTAGTCGCTGTTGGATCGGGTTCTAAAGG CGCTG CTGGT TTTAGAACCCGAAAGGGTGGAGAGATTCAACCAGTTAGCGTGAA HSPG2 NM_005529 1129 GAGTACGTGTGCC1130 CTCAATGGTGACCAG 1131 CAGCTCCGTGCCTC 1132GAGTACGTGTGCCGAGTGTTGGGCAGCTCCGTGCCT TAGAGG ICAM1 NM_000201 1133GCAGACAGTGACCAT 1134 CTTCTGAGACCTCTGG 1135 CCGGCGCCCAACGT 1136GCAGACAGTGACCATCTACAGCTTTCCGGCGCCCAACGT CTACAGCTT CTTCGT GATTCTGATTCTGACGAAGCCAGAGGTCTCAGAAG IER3 NM_003897 1137 GTACCTGGTGCGCGA 1138GCGTCTCCGCTGTAGT 1139 TCAAGTTGCCTCGG 1140GTACCTGGTGCGCGAGAGCGTATCCCCAACTGGGACTTC GAG GTT AAGTCCCAGTCGAGGCAACTTGAACTCAGAACACTACAGCGGA IFI30 NM_006332 1141 ATCCCATGAAGCC1142 GCACCATTCTTAGTG 1143 AAAATTCCACCCCA 1144ATCCCATGAAGCCCAGATACACAAAATTCCACCCCA TGATCA IFIT1 NM_001548 1145TGACAACCAAGCA 1146 CAGTCTGCCCATGTG 1147 AAGTTGCCCCAGGT 1148TGACAACCAAGCAAATGTGAGGAGTCTGGTGACCTG CACCAG IFNG NM_000619 1149GCTAAAACAGGGAAG 1150 CAACCATTACTGGGAT 1151 TCGACCTCGAAACA 1152GCTAAAACAGGGAAGCGAAAAAGGAGTCAGATGCTGTTT CGAAA GCTC GCATCTGACTCCCGAGGTCGAAGAGCATCCCAGTAATGGTTG IGF1 NM_000618 1153 TCCGGAGCTGTGA 1154CGGACAGAGCGAGCT 1155 TGTATTGCGCACCC 1156TCCGGAGCTGTGATCTAAGGAGGCTGGAGATGTATT CTCAAG IGF1R NM_000875 1157GCATGGTAGCCGAAG 1158 TTTCCGGTAATAGTCT 1159 CGCGTCATACCAAA 1160GCATGGTAGCCGAAGATTTCACAGTCAAAATCGGAGATT ATTTCA GTCTCATAGATATCATCTCCGATTTTGA TTGGTATGACGCGAGATATCTATGAGACAGACTA IGF2 NM_000612 1161CCGTGCTTCCGGA 1162 TGGACTGCTTCCAGG 1163 TACCCCGTGGGCAA 1164CCGTGCTTCCGGACAACTTCCCCAGATACCCCGTGGG GTTCTT IGFBP2 NM_000597 1165GTGGACAGCACCA 1166 CCTTCATACCCGACTT 1167 CTTCCGGCCAGCAC 1168GTGGACAGCACCATGAACATGTTGGGCGGGGGAGGC TGCCTC IGFBP3 NM_000598 1169ACATCCCAACGCA 1170 CCACGCCCTTGTTTCA 1171 ACACCACAGAAGGC 1172ACATCCCAACGCATGCTCCTGGAGCTCACAGCCTTCT TGTGA IGFBP5 NM_000599 1173TGGACAAGTACGG 1174 CGAAGGTGTGGCACT 1175 CCCGTCAACGTACT 1176TGGACAAGTACGGGATGAAGCTGCCAGGCATGGAGT CCATGC IGFBP6 NM_002178 1177TGAACCGCAGAGACC 1178 GTCTTGGACACCCGCA 1179 ATCCAGGCACCTCT 1180TGAACCGCAGAGACCAACAGAGGAATCCAGGCACCTCTA AACAG GAAT ACCACGCCCTCCCACGCCCTCCCAGCCCAATTCTGCGGGTGTCCA IL10 NM_000572 1181 CTGACCACGCTTT1182 CCAAGCCCAGAGACA 1183 TTGAGCTGTTTTCC 1184CTGACCACGCTTTCTAGCTGTTGAGCTGTTTTCCCTG CTGACC IL11 NM_000641 1185TGGAAGGTTCCAC 1186 TCTTGACCTTGCAGCT 1187 CCTGTGATCAACAG 1188TGGAAGGTTCCACAAGTCACCCTGTGATCAACAGTA TACCCG IL17A NM_002190 1189TCAAGCAACACTC 1190 CAGCTCCTTTCTGGGT 1191 TGGCTTCTGTCTGA 1192TCAAGCAACACTCCTAGGGCCTGGCTTCTGTCTGATC TCAAGG IL1A NM_000575 1193GGTCCTTGGTAGA 1194 GGATGGAGCTTCAGG 1195 TCTCCACCCTGGCC 1196GGTCCTTGGTAGAGGGCTACTTTACTGTAACAGGGC CTGTTA IL1B NM_000576 1197AGCTGAGGAAGAT 1198 GGAAAGAAGGTGCTC 1199 TGCCCACAGACCTT 1200AGCTGAGGAAGATGCTGGTTCCCTGCCCACAGACCT CCAGGA IL2 NM_000586 1201ACCTCAACTCCTGCC 1202 CACTGTTTGTGACAAG 1203 TGCAACTCCTGTCT 1204ACCTCAACTCCTGCCACAATGTACAGGATGCAACTCCTG ACAAT TGCAAG TGCATTGCACTCTTGCATTGCACTAAGTCTTGCACTTGTCACAAA IL6 NM_000600 1205 CCTGAACCTTCCA1206 ACCAGGCAAGTCTCC 1207 CCAGATTGGAAGCA 1208CCTGAACCTTCCAAAGATGGCTGAAAAAGATGGATG TCCATC IL6R NM_000565 1209CCAGCTTATCTCA 1210 CTGGCGTAGAACCTT 1211 CCTTTGGCTTCACG 1212CCAGCTTATCTCAGGGGTGTGCGGCCTTTGGCTTCAC GAAGAG IL6ST NM_002184 1213GGCCTAATGTTCC 1214 AAAATTGTGCCTTGG 1215 CATATTGCCCAGTG 1216GGCCTAATGTTCCAGATCCTTCAAAGAGTCATATTGC GTCACC IL8 NM_000584 1217AAGGAACCATCTCAC 1218 ATCAGGAAGGCTGCCA 1219 TGACTTCCAAGCTG 1220AAGGAACCATCTCACTGTGTGTAAACATGACTTCCAAGC TGTGTGTAAAC AGAG GCCGTGGCTGGCCGTGGCTCTCTTGGCAGCCTTCCTGAT ILF3 NM_004516 1221 GACACGCCAAGTG 1222CTCAAGACCCGGATC 1223 ACACAAGACTTCAG 1224GACACGCCAAGTGGTTCCAGGCCAGAGCCAACGGGC CCCGTT ILK NM_001014794 1225CTCAGGATTTTCTCG 1226 AGGAGCAGGTGGAGAC 1227 ATGTGCTCCCAGTG 1228CTCAGGATTTTCTCGCATCCAAATGTGCTCCCAGTGCTA CATCC TGG CTAGGTGCCTGGTGCCTGCCAGTCTCCACCTGCTCCT IMMT NM_006839 1229 CTGCCTATGCCAG 1230GCTTTTCTGGCTTCCT 1231 CAACTGCATGGCTC 1232CTGCCTATGCCAGACTCAGAGGAATCGAACAGGCTG TGAACA ING5 NM_032329 1233CCTACAGCAAGTG 1234 CATCTCGTAGGTCTG 1235 CCAGCTGCACTTTG 1236CCTACAGCAAGTGCAAGGAATACAGTGACGACAAAG TCGTCA INHBA NM_002192 1237GTGCCCGAGCCAT 1238 CGGTAGTGGTTGATG 1239 ACGTCCGGGTCCTC 1240GTGCCCGAGCCATATAGCAGGCACGTCCGGGTCCTC ACTGTC INSL4 NM_002195 1241CTGTCATATTGCCC 1242 CAGATTCCAGCAGCC 1243 TGAGAAGACATTCA 1244CTGTCATATTGCCCCATGCCTGAGAAGACATTCACCA CCACCA ITGA1 NM_181501 1245GCTTCTTCTGGAG 1246 CCTGTAGATAATGAC 1247 TTGCTGGACAGCCT 1248GCTTCTTCTGGAGATGTGCTCTATATTGCTGGACAGC CGGTAC ITGA3 NM_002204 1249CCATGATCCTCAC 1250 GAAGCTTTGTAGCCG 1251 CACTCCAGACCTCG 1252CCATGATCCTCACTCTGCTGGTGGACTATACACACTCCA CTTAGC ITGA4 NM_000885 1253CAACGCTTCAGTG 1254 GTCTGGCCGGGATTC 1255 CGATCCTGCATCTG 1256CAACGCTTCAGTGATCAATCCCGGGGCGATTTACAG TAAATC ITGA5 NM_002205 1257AGGCCAGCCCTAC 1258 GTCTTCTCCACAGTCC 1259 TCTGAGCCTTGTCC 1260AGGCCAGCCCTACATTATCAGAGCAAGAGCCGGATA TCTATC ITGA6 NM_000210 1261CAGTGACAAACAG 1262 GTTTAGCCTCATGGG 1263 TCGCCATCTTTTGT 1264CAGTGACAAACAGCCCTTCCAACCCAAGGAATCCCA GGGATT ITGA7 NM_002206 1265GATATGATTGGTCGC 1266 AGAACTTCCATTCCCC 1267 CAGCCAGGACCTGG 1268GATATGATTGGTCGCTGCTTTGTGCTCAGCCAGGACCTG TGCTTTG ACCAT CCATCCGGCCATCCGGGATGAGTTGGATGGTGGGGAATGGA ITGAD NM_005353 1269 GAGCCTGGTGGAT1270 ACTGTCAGGATGCCC 1271 CAACTGAAAGGCCT 1272GAGCCTGGTGGATCCCATCGTCCAACTGAAAGGCCT GACGTT ITGB3 NM_000212 1273ACCGGGAGCCCTACA 1274 CCTTAAGCTCTTTCAC 1275 AAATACCTGCAACC 1276ACCGGGGAGCCCTACATGACGAAAATACCTGCAACCGTT TGAC TGACTCAATCT GTTACTGCCGTGACACTGCCGTGACGAGATTGAGTCAGTGAAAGAGC ITGB4 NM_000213 1277 CAAGGTGCCCTCA1278 GCGCACACCTTCATC 1279 CACCAACCTGTACC 1280CAAGGTGCCCTCAGTGGAGCTCACCAACCTGTACCC CGTATT ITGB5 NM_002213 1281TCGTGAAAGATGA 1282 GGTGAACATCATGAC 1283 TGCTATGTTTCTAC 1284TCGTGAAAGATGACCAGGAGGCTGTGCTATGTTTCTA AAAACC ITPR1 NM_002222 1285GAGGAGGTGTGGG 1286 GTAATCCCATGTCCG 1287 CCATCCTAACGGAA 1288GAGGAGGTGTGGGTGTTCCGCTTCCATCCTAACGGA CGAGCT ITPR3 NM_002224 1289TTGCCATCGTGTC 1290 ATGGAGCTGGCGTCA 1291 TCCAGGTCTCGGAT 1292TTGCCATCGTGTCAGTGCCCGTGTCTGAGATCCGAGA CTCAGA ITSN1 NM_003024 1293TAACTGGGATGCA 1294 CTCTGCCTTAACTGGC 1295 AGCCCTCTCTCACC 1296TAACTGGGATGCATGGGCAGCCCAGCCCTCTCTCAC GTTCCA JAG1 NM_000214 1297TGGCTTACACTGG 1298 GCATAGCTGTGAGAT 1299 ACTCGATTTCCCAG 1300TGGCTTACACTGGCAATGGTAGTTTCTGTGGTTGGCT CCAACC JUN NM_002228 1301GACTGCAAAGATGGA 1302 TAGCCATAAGGTCCGC 1303 CTATGACGATGCCC 1304GACTGCAAAGATGGAAACGACCTTCTATGACGATGCCCT AACGA TCTC TCAACGCCTCCAACGCCTCGTTCCTCCCGTCCGAGAGCGGACCT JUNB NM_002229 1305 CTGTCAGCTGCTG1306 AGGGGGTGTCCGTAA 1307 CAAGGGACACGCCT 1308CTGTCAGCTGCTGCTTGGGGTCAAGGGACACGCCTT TCTGAA KCNN2 NM_021614 1309TGTGCTATTCATCC 1310 GGGCATAGGAGAAGG 1311 TTATACATTCACAT 1312TGTGCTATTCATCCCATACCTGGGAATTATACATTCA GGACGG KCTD12 NM_138444 1313AGCAGTTACTGGC 1314 TGGAGACCTGAGCAG 1315 ACTCTTAGGCGGCA 1316AGCAGTTACTGGCAAGAGGGAGAAAGGACGCTGCCG GCGTCC KHDRBS NM_006558 1317CGGGCAAGAAGAG 1318 CTGTAGACGCCCTTT 1319 CAAGACACAAGGCA 1320CGGGCAAGAAGAGTGGACTAACTCAAGACACAAGGC CCTTCA KIAA019 NM_014846 1321CAGACACCAGCTC 1322 AACATTGTGAGGCGG 1323 TCCCCAGTGTCCAG 1324CAGACACCAGCTCTGAGGCCAGTTAATCATCCCCAG GCACAG KIAA024 NM_014734 1325CCGTGGGACATGG 1326 GAAGCAAGTCCGTCT 1327 TCCGCTAGTGATCC 1328CCGTGGGACATGGAGTGTTCCTTCCGCTAGTGATCCT TTTGCA KIF4A NM_012310 1329AGAGCTGTCTCC 1330 GCTGGTCTTGCTCTGT 1331 CAGGTCAGCAAACT 1332AGAGCTGGTCTCCTCCAAAATACAGGTCAGCAAACT TGAAAG KIT NM_000222 1333GAGGCAACTGCTTAT 1334 GGCACTCGGCTTGAGC 1335 TTACAGCGACAGTC 1336GAGGCAACTGCTTATGGCTTAATTAAGTCAGATGCGGCC GGCTTAATTA AT ATGGCCGCATATGACTGTCGCTGTAAAGATGCTCAAGCCGAGT KLC1 NM_182923 1337 AGTGGCTACGGGA 1338TGAGCCACAGACTGC 1339 CAACACGCAGCAGA 1340AGTGGCTACGGGATGAACTGGCCAACACGCAGCAGA AACTG KLF6 NM_001300 1341CACGAGACCGGCT 1342 GCTCTAGGCAGGTCT 1343 AGTACTCCTCCAGA 1344CACGAGACCGGCTACTTCTCGGCGCTGCCGTCTCTGG GACGGC KLK1 NM_002257 1345AACACAGCCCAGTTT 1346 CCAGGAGGCTCATGTT 1347 TCAGTGAGAGCTTC 1348AACACAGCCCAGTTTGTTCATGTCAGTGAGAGCTTCCCA GTTCA GAAG CCACACCCTGCACCCTGGCTTCAACATGAGCCTCCTGG KLK10 NM_002776 1349 GCCCAGAGGCTCC 1350CAGAGGTTTGAACAG 1351 CCTCTTCCTCCCCA 1352GCCCAGAGGCTCCATCGTCCATCCTCTTCCTCCCCAG GTCGGC KLK11 NM_006853 1353CACCCCGGCTTCA 1354 CATCTTCACCAGCAT 1355 CCTCCCCAACAAAG 1356CACCCCGGCTTCAACAACAGCCTCCCCAACAAAGAC ACCACC KLK14 NM_022046 1357CCCCTAAAATGTT 1358 CTCATCCTCTTGGCTC 1359 CAGCACTTCAAGTC 1360CCCCTAAAATGTTCCTCCTGCTGACAGCACTTCAAGT CTGGCT KLK2 NM_005551 1361AGTCTCGGATTGT 1362 TGTACACAGCCACCT 1363 TTGGGAATGCTTCT 1364AGTCTCGGATTGTGGGAGGCTGGGAGTGTGAGAAGC CACACT KLK3 NM_001648 1365CCAAGCTTACCAC 1366 AGGGTGAGGAAGACA 1367 ACCCACATGGTGAC 1368CCAAGCTTACCACCTGCACCCGGAGAGCTGTGTCAC ACAGCT KLRK1 NM_007360 1369TGAGAGCCAGGCT 1370 ATCCTGGTCCTCTTTG 1371 TGTCTCAAAATGCC 1372TGAGAGCCAGGCTTCTTGTATGTCTCAAAATGCCAGC AGCCTT KPNA2 NM_002266 1373TGATGGTCCAAAT 1374 AAGCTTCACAAGTTG 1375 ACTCCTGTTTTCAC 1376TGATGGTCCAAATGAACGAATTGGCATGGTGGTGAA CACCAT KRT1 NM_006121 1377TGGACAACAACCG 1378 TATCCTCGTACTGGG 1379 CCTCAGCAATGATG 1380TGGACAACAACCGCAGTCTCGACCTGGACAGCATCA CTGTCC KRT15 NM_002275 1381GCCTGGTTCTTCA 1382 CTTGCTGGTCTGGATC 1383 TGAACAAAGAGGTG 1384GCCTGGTTCTTCAGCAAGACTGAGGAGCTGAACAAA GCCTCC KRT18 NM_000224 1385AGAGATCGAGGCT 1386 GGCCTTTTACTTCCTC 1387 TGGTTCTTCTTCAT 1388AGAGATCGAGGCTCTCAAGGAGGAGCTGCTCTTCAT GAAGAG KRT2 NM_000423 1389CCAGTGACGCCTC 1390 GGGCATGGCTAGAAG 1391 ACCTAGACAGCACA 1392CCAGTGACGCCTCTGTGTTCTGGGGCGGAATCTGTGC GATTCC KRT5 NM_000424 1393TCAGTGGAGAAGG 1394 TGCCATATCCAGAGG 1395 CCAGTCAACATCTC 1396TCAGTGGAGAAGGAGTTGGACCAGTCAACATCTCTG TGTTGT KRT75 NM_004693 1397TCAAAGTCAGGTACG 1398 ACGCTCCTTTTTCAGG 1399 TTCATTCTCAGCAG 1400TCAAAGTCAGGTACGAAGATGAAATTAACAAGCGCACAG AAGATGAAATT GCTACAA CTGTGCGCTTGTCTGCTGAGAATGAATTTGTAGCCCTGAAAAAGG KRT76 NM_015848 1401 ATCTCCAGACTGCTG1402 TCAGGGAATTAGGGGA 1403 TCTGGGCTTCAGAT 1404ATCTCCAGACTGCTGGTTCCCAGGGAACCCTCCCTACAT GTTCC CAGA CCTGACTCCCCTGGGCTTCAGATCCTGACTCCCTTCTGTCCCCTA KRT8 NM_002273 1405 GGATGAAGCTTACAT1406 CATATAGCTGCCTGAG 1407 CGTCGGTCAGCCCT 1408GGATGAAGCTTACATGAACAAGGTAGAGCTGGAGTCTCG GAACAAGGTAG GAAGTTGAT TCCAGGCCCTGGAAGGGCTGACCGACGAGATCAACTTCCT L1CAM NM_000425 1409 CTTGCTGGCCAAT1410 TGATTGTCCGCAGTC 1411 ATCTACGTTGTCCA 1412CTTGCTGGCCAATGCCTACATCTACGTTGTCCAGCTG GCTGCC LAG3 NM_002286 1413GCCTTAGAGCAAG 1414 CGGTTCTTGCTCCAGC 1415 TCTATCTTGCTCTG 1416GCCTTAGAGCAAGGGATTCACCCTCCGCAGGCTCAG AGCCTG LAMA3 NM_000227 1417CCTGTCACTGAAG 1418 TGGGTTACTGGTCAG 1419 ATTCAGACTGACAG 1420CCTGTCACTGAAGCCTTGGAAGTCCAGGGGCCTGTC GCCCCT LAMA4 NM_002290 1421GATGCACTGCGGT 1422 CAGAGGATACGCTCA 1423 CTCTCCATCGAGGA 1424GATGCACTGCGGTTAGCAGCGCTCTCCATCGAGGAA AGGCAA LAMA5 NM_005560 1425CTCCTGGCCAACA 1426 ACACAAGGCCCAGCC 1427 CTGTTCCTGGAGCA 1428CTCCTGGCCAACAGCACTGCACTAGAAGAGGCCATG TGGCCT LAMB1 NM_002291 1429CAAGGAGACTGGG 1430 CGGCAGAACTGACAG 1431 CAAGTGCCTGTACC 1432CAAGGAGACTGGGAGGTGTCTCAAGTGCCTGTACCA ACACGG LABM3 NM_000228 1433ACTGACCAAGCCT 1434 GTCACACTTGCAGCA 1435 CCACTCGCCATACT 1436ACTGACCAAGCCTGAGACCTACTGCACCCAGTATGG GGGTGC LAMC1 NM_002293 1437GCCGTGATCTCAG 1438 ACCTGCTTGCCCAAG 1439 CCTCGGTACTTCAT 1440GCCGTGATCTCAGACAGCTACTTTCCTCGGTACTTCA TGCTCC LAMC2 NM_005562 1441ACTCAAGCGGAAATT 1442 ACTCCCTGAAGCCGAG 1443 AGGTCTTATCAGCA 1444ACTCAAGCGGAAATTGAAGCAGATAGGTCTTATCAGCAC GAAGCA ACACT CAGTCTCCGCCTCCAGTCTCCGCCTCCTGGATTCAGTGTCTCGGCTTC LAPTM5 NM_006762 1445 TGCTGGACTTCTG1446 TGAGATAGGTGGGCA 1447 TCCTGACCCTCTGC 1448TGCTGGACTTCTGCCTGAGCATCCTGACCCTCTGCAG AGCTCC LGALS3 NM_002306 1449AGCGGAAAATGGC 1450 CTTGAGGGTTTGGGT 1451 ACCCAGATAACGCA 1452AGCGGAAAATGGCAGACAATTTTTCGCTCCATGATG TCATGG LIG3 NM_002311 1453GGAGGTGGAGAAG 1454 ACAGGTGTCATAGC 1455 CTGGACGCTCAGAG 1456GGAGGTGGAGAAGGAGCCGGGCCAGAGACGAGCTCT CTCGTC LIMS1 NM_004987 1457TGAACAGTAATGG 1458 TTCTGGGAACTGCTG 1459 ACTGAGCGCACACG 1460TGAACAGTAATGGGGAGCTGTACCATGAGCAGTGTT AAACA LOX NM_002317 1461CCAATGGGAGAAC 1462 CGCTGAGGCTGGTAC 1463 CAGGCTCAGCAAGC 1464CCAATGGGAGAACAACGGGCAGGTGTTCAGCTTGCT TGAACA LRP1 NM_002332 1465TTTGGCCCAATGGGC 1466 GTCTCGATGCGGTCGT 1467 TCCCGGCTGGGCGC 1468TTTGGCCCAATGGGCTAAGCCTGGACATCCCGGCTGGGC TAAG AGAAG CTCTACTGCCTCTACTGGGTGGATGCCTTCTACGACCGCAT LTBP2 NM_000428 1469 GCACACCCATCCT1470 GATGGCTGGCCACGT 1471 CTTTGCAGCCCTCA 1472GCACACCCATCCTTGAGTCTCCTTTGCAGCCCTCAGA GAACTC LUM NM_002345 1473GGCTCTTTTGAAGGA 1474 AAAAGCAGCTGAAACA 1475 CCTGACCTTCATCC 1476GGCTCTTTTGAAGGATTGGTAAACCTGACCTTCATCCAT TTGGTAA GCATC ATCTCCAGCACTCCAGCACAATCGGCTGAAAGAGGATGCTGTTT MAGEA4 NM_002362 1477 GCATCTAACAGCC1478 CAGAGTGAAGAATGG 1479 CAGCTTCCCTTGCC 1480GCATCTAACAGCCCTGTGCAGCAGCTTCCCTTGCCTC TCGTGT MANF NM_006010 1481CAGATGTGAAGCC 1482 AAGGGAATCCCCTCA 1483 TTCCTGATGATGCT 1484CAGATGTGAAGCCTGGAGCTTTCCTGATGATGCTGG GGCCCT MAOA NM_000240 1485GTGTCAGCCAAAG 1486 CGACTACGTCGAACA 1487 CCGCGATACTCGCC 1488GTGTCAGCCAAAGCATGGAGAATCAAGAGAAGGCGA TTCTCT MAP3K5 NM_005923 1489AGGACCAAGAGGC 1490 CCTGTGGCCATTTCA 1491 CAGCCCAGAGACCA 1492AGGACCAAGAGGCTACGGAAAAGCAGCAGACATCTG GATGTC MAP3K7 NM_145333 1493CAGGCAAGAACTAGT 1494 CCTGTACCAGGCGAGA 1495 TGCTGGTCCTTTTC 1496CAGGCAAGAACTAGTTGCAGAACTGGACCAGGATGAAAA TGCAGAA TGTAT ATCCTGGTCCGGACCAGCAAAATACATCTCGCCTGGTACAGG MAP4K4 NM_004834 1497 TCGCCGAGATTTC1498 CTGTTGTCTCCGAAG 1499 AACGTTCCTTGTTC 1500TCGCCGAGATTTCCTGAGACTGCAGCAGGAGAACAA TCCTGC MAP7 NM_003980 1501GAGGAACAGAGGT 1502 CTGCCAACTGGCTTTC 1503 CATGTACAACAAAC 1504GAGGAACAGAGGTGTCTGCACTTCCATGTACAACAA GCTCCG MAPKAPK3 NM_004635 1505AAGCTGCAGAGATAA 1506 GTGGGCAATGTTATGG 1507 ATTGGCACTGCCAT 1508AAGCTGCAGAGATAATGCGGGATATTGGCACTGCCATCC TGCGG CTG CCAGTTTCTGAGTTTCTGCACAGCCATAACATTGCCCAC MCM2 NM_004526 1509 GACTTTTGCCCGCTA 1510GCCACTAACTGCTTCA 1511 ACAGCTCATTGTTG 1512GACTTTTGCCCGCTACCTTTCATTCCGCGTGACAACAAT CCTTTC GTATGAAGAG TCACGCCGGAGAGCTGTTGCTCTTCATACTGAAGCAGTTAGTGG MCM3 NM_002388 1513 GGAGAACAATCCC1514 ATCTCCTGGATGGTG 1515 TGGCCTTTCTGTCT 1516GGAGAACAATCCCCTTGAGACAGAATATGGCCTTTC ACAAGG MCM6 NM_005915 1517TGATGGTCCTATGTG 1518 TGGGACAGGAAACACA 1519 CAGGTTTCATACCA 1520TGATGGTCCTATGTGTCACATTCATCACAGGTTTCATAC TCACATTCA CCAA ACACAGGCTTCAGCCAACACAGGCTTCAGCACTTCCTTTGGTGTGTTTC MDK NM_002391 1521 GGAGCCGACGTGCA1522 GACTTTGGTGCCTGT 1523 ATCACACGCACCCC 1524GGAGCCGACTGCAAGTACAAGTTTGAGAACTGGGGT AGTTCT MDM2 NM_002392 1525CTACAGGGACGCC 1526 ATCCAACCAATCACC 1527 CTTACACCAGCATC 1528CTACAGGGACGCCATCGAATCCGGATCTTGATGCTG AAGATC MELK NM_014791 1529AGGATCGCCTGTC 1530 TGCACATAAGCAACA 1531 CCCGGGTTGTCTTC 1532AGGATCGCCTGTCAGAAGAGGAGACCCGGGTTGTCT CGTCAG MET NM_000245 1533GACATTTCCAGTCCT 1534 CTCCGATCGCACACAT 1535 TGCCTCTCTGCCCC 1536GACATTTCCAGTCCTGCAGTCAATGCCTCTCTGCCCCAC GCAGTCA TTGT ACCCTTTGTCCTTTGTTCAGTGTGGCTGGTGCCACGACAAATGT MGMT NM_002412 1537 GTGAAATGAAACG1538 GACCCTGCTCACAAC 1539 CAGCCCTTTGGGGA 1540GTGAAATGAAACGCACCACACTGGACAGCCCTTTGG AGCTGG MGST1 NM_020300 1541ACGGATCTACCACAC 1542 TCCATATCCAACAAAA 1543 TTTGACACCCCTTC 1544ACGGATCTACCACACCATTGCATATTTGACACCCCTTCC CATTGC AAACTCAAAG CCCAGCCACCAGCCAAATAGAGCTTTGAGTTTTTTTGTTGGAT MICA NM_000247 1545 ATGGTGAATGTCA1546 AAGCCAGAAGCCCTG 1547 CGAGGCCTCAGAGG 1548ATGGTGAATGTCACCCGCAGCGAGGCCTCAGAGGGC GCAAC MKI67 NM_002417 1549GATTGCACCAGGG 1550 TCCAAAGTGCCTCTG 1551 CCACTCTTCCTTGA 1552GATTGCACCAGGGCAGAACAGGGGAGGGTGTTCAAG ACACCC MLXIP NM_014938 1553TGCTTAGCTGGCA 1554 CAGCCTACTCTCCAT 1555 CATGAGATGCCAGG 1556TGCTTAGCTGGCATGTGGCCGCATGAGATGCCAGGA AGACCC MMP11 NM_005940 1557CCTGGAGGCTGCAAC 1558 TACAATGGCTTTGGAG 1559 ATCCTCCTGAAGCC 1560CCTGGAGGCTGCAACATACCTCAATCCTGTCCCAGGCCG ATACC GATAGCA CTTTTCGCAGCGATCCTCCTGAAGCCCTTTTCGCAGCACTGCTAT MMP2 NM_004530 1561 CAGCCAGAAGCGG1562 AGACACCATCACCTG 1563 AAGTCCGAATCTCT 1564CAGCCAGAAGCGGAAACCTTAAAAAGTCCGATCTCT GCTCCC MMP7 NM_002423 1565GGATGGTAGCAGTCT 1566 GGAATGTCCCATACCC 1567 CCTGTATGCTGCAA 1568GGATGGTAGCAGTCTAGGGATTAACTTCCTGTATGCTGC AGGGATTAACT AAAGAACTCATGAACTTGGC AACTCATGAACTTGGCCATTCTTTGGGTATGGGAC MMP9 NM_004994 1569GAGAACCAATCTC 1570 CACCCGAGTGTAACC 1571 ACAGGTATTCCTCT 1572GAGAACCAATCTCACCGACAGGCAGCTGGCAGAGGA GCCAGC MPPED2 NM_001584 1573CCGACCAACCCTC 1574 AGGGCATTTAGAGCT 1575 ATTTGACCTTCCAA 1576CCGACCAACCCTCCAATTATATTTGACCTTCCAAACC ACCCAC MRC1 NM_002438 1577CTTGACCTCAGGA 1578 GGACTGCGGTCACTC 1579 CCAACCGCTGTTGA 1580CTTGACCTCAGGACTCTGGATTGGACTTAACAGTCTG AGCTCA MRPL13 NM_014078 1581TCCGGTTCCCTTCG 1582 GTGGAAAAACTGCGG 1583 CGGCTGGAAATTAT 1584TCCGGTTCCCTTCGTTTAGGTCGGCTGGAAATTATGT GTCCTC MSH2 NM_000251 1585GATGCAGAATTGA 1586 TCTTGGCAAGTCGGT 1587 CAAGAAGATTTACT 1588GATGCAGAATTGAGGCAGACTTTACAAGAAGATTTA TCGTCG MSH3 NM_002439 1589TGATTACCATCATGG 1590 CTTGTGAAAATGCCAT 1591 TCCCAATTGTCGCT 1592TGATTACCATCATGGCTCAGATTGGCTCCTATGTTCCTG CTCAGA CCAC TCTTCTGCAGCAGAAGAAGCGACAATTGGGATTGTGGATGGCAT MSH6 NM_000179 1593 TCTATTGGGGGAT1594 CAAATTGCGAGTGGT 1595 CCGTTACCAGCTGG 1596TCTATTGGGGGATTGGTAGGAACCGTTACCAGCTGG AAATTC MTA1 NM_004689 1597CCGCCCTCACCTGAA 1598 GGAATAAGTTAGCCGC 1599 CCCAGTGTCCGCCA 1600CCGCCCTCACCTGCAGAGAAACGCGCTCCTTGGCGGACA GAGA GCTTCT AGGAGCGCTGGGGGAGGAGAGGAAGAAGCGCGGCTAACTT MTPN NM_145808 1601 GGTGGAAGGAAAC 1602CAGCAGCAGAAATTC 1603 AAGCTGCCCACAAT 1604GGTGGAAGGAAACCTCTTCATTATGCAGCAGATTGT CTGCTG MTSS1 NM_014751 1605TTCGACAAGTCCT 1606 CTTGGAACATCCGTC 1607 CCAAGAAACAGCGA 1608TTCGACAAGTCCTCCACCATTCCAAGAAACAGCGAC CATCA MUC1 NM_002456 1609GGCCAGGATCTGTGG 1610 CTCCACGTCGTGGACA 1611 CTCTGGCCTTCCGA 1612GGCCAGGATCTGTGGTGGTACAATTGACTCTGGCCTTCC TGGTA TTGA GAAGGTACCGAGAAGGTACCATCAATGTCCACGACGTGGAG MVP NM_017458 1613 ACGAGAACGAGGGCA 1614GCATGTAGGTGCTTCC 1615 CGCACCTTTCCGGT 1616ACGAGAACGAGGGCATCTATGTGCAGGATGTCAAGACCG TCTATGT AATCAC CTTGACATCCTGAAAGGTGCGCGCTGTGATTGGAAGCACCTACA MYBL2 NM_002466 1617 GCCGAGATCGCCAAG1618 CTTTTGATGGTAGAGT 1619 CAGCATTGTCTGTC 1620GCCGAGATCGCCAAGATGTTGCCAGGGAGGACAGACAAT ATG TCCAGTGATTC CTCCCTGGCAGCTGTGAAGAATCACTGGAACTCTACCATCAAA MYBPC1 NM_002465 1621 CAGCAACCAGGGA1622 CAGCAGTAAGTGCCT 1623 AAATTCGCAAGCCC 1624CAGCAACCAGGGAGTCTGTACCCTGGAAATTCGCAA AGCCCC MYC NM_002467 1625TCCCTCCACTCGGAA 1626 CGGTTGTTGCTGATCT 1627 TCTGACACTGTCCA 1628TCCCTCCACTCGGAAGGACTATCCTGCTGCCAAGAGGGT GGACTA GTCTCA ACTTGACCCTCTTCAAGTTGGACAGTGTCAGAGTCCTGAGACAGAT MYLK3 NM_182493 1629 CACCTGACTGAGCTG1630 GATGTAGTGCTGGTGC 1631 CACACCCTCACAGA 1632CACCTGACTGAGCTGGATGTGGTCCTGTTCACCAGGCAG GATGT AGGT TCTGCCTGGTATCTGTGAGGGTGTGCATTACCTGCACCAGCACT MYO6 NM_004999 1633 AAGCAGTTCTGGA1634 GATGAGCTCGGCTTC 1635 CAATCCTCAGGGCC 1636AAGCAGTTCTGGAGCAGGAGCGCAGGGACCGGGAGC AGCTCC NCAM1 NM_000615 1637TAGTTCCCAGCTG 1638 CAGCCTTGTTCTCAGC 1639 CTCAGCCTCGTCGT 1640TAGTTCCCAGCTGACCATCAAAAAGGTGGATAAGAA TCTTAT NCAPD3 NM_015261 1641TCGTTGCTTAGAC 1642 CTCCAGACAGTGTGC 1643 CTACTGTCCGCAGC 1644TCGTTGCTTAGACAAGGCGCCTACTGTCCGCAGCAA AAGGCA NCOR1 NM_006311 1645AACCGTTACAGCC 1646 TCTGGAGAGACCCTT 1647 CCAGGCTCAGTCTG 1648AACCGTTACAGCCCAGAATCCCAGGCTCAGTCTGTCC TCCATC NCOR2 NM_006312 1649CGTCATCTACGAA 1650 GAGCACTGGGTCACA 1651 CCTCATAGGACAAG 1652CGTCATCTACGAAGGCAAGAAGGGCCACGTCTTGTC ACGTGG NDRG1 NM_006096 1653AGGGCAACATTCC 1654 CAGTGCTCCTACTCC 1655 CTGCAAGGACACTC 1656AGGGCAACATTCCACAGCTGCCCTGGCTGTGATGAG ATCACA NDUFS5 NM_004552 1657AGAAGAGTCAAGG 1658 AGGCCGAACCTTTTC 1659 TGTCCAAGAAAGGC 1660AGAAGAGTCAAGGGCACGAGCATCGGGTAGCCATGC ATGGCT NEK2 NM_002497 1661GTGAGGCAGCGCGAC 1662 TGCCAATGGTGTACAA 1663 TGCCTTCCCGGGCT 1664GTGAGGCAGCGCGACTCTGGCGACTGGCCGGCCATGCCT TCT CACTTCA GAGGACTTCCCGGGCTGAGGACTATGAAGTGTTGTACACC NETO2 NM_018092 1665 CCAGGGCACCATA1666 AACGGTAAATCAAGG 1667 AGCCAACCCTTTTC 1668CCAGGGCACCATACTGTTTCCAGCAGCCAACCCTTTT TCCCAT NEXN NM_144573 1669AGGAGGAGGAAGA 1670 GAGCTCCTGATCTGG 1671 TCATCTTCAGCAGT 1672AGGAGGAGGAAGAAGGTAGCATCATGAATGGCTCCA GGAGCC NFAT5 NM_006599 1673CTGAACCCCTCTC 1674 AGGAAACGATGGCGA 1675 CGAGAATCAGTCCC 1676CTGAACCCCTCTCCTGGTCACCGAGAATCAGTCCCCG CGTGGA NFATC2 NM_173091 1677CAGTCAAGGTCAG 1678 CTTTGGCTCGTGGCAT 1679 CGGGTTCCTACCCC 1680CAGTCAAGGTCAGAGGCTGAGCCCGGGTTCCTACCC ACAGTC NFKB1 NM_003998 1681CAGACCAAGGAGA 1682 AGCTGCCAGTGCTAT 1683 AAGCTGTAAACATG 1684CAGACCAAGGAGATGGACCTCAGCGTGGTGCGGCTC AGCCGC NFKBIA NM_020529 1685C TACTGGACGACC 1686 CCTTGACCATCTGCTC 1687 CTCGTCTTTCATGG 1688CTACTGGACGACCGCCACGACAGCGGCCTGGACTCC AGTCCA NME1 NM_000269 1689CCAACCCTGCAGACT 1690 ATGTATAATGTTCCTG 1691 CCTGGGACCATCCG 1692CCAACCCTGCAGACTCCAAGCCTGGGACCATCCGTGGAG CCAA CCAACTTGTATG TGGAGACTTCTACTTCTGCATACAAGTTGGCAGGAACATTATAC NNMT NM_006169 1693 CCTAGGGCAGGGA 1694CTAGTCCAGCCAAAC 1695 CCCTCTCCTCATGC 1696CCTAGGGCAGGGATGGAGAGAGAGTCTGGGCATGAG CCAGAC NOS3 NM_000603 1697ATCTCCGCCTCGC 1698 TCGGAGCCATACAGG 1699 TTCACTCGCTTCGC 1700ATCTCCGCCTCGCTCATGGGCACGGTGATGGCGAAG CATCAC NOX4 NM_016931 1701CCTCAACTGCAGCCT 1702 TGCTTGGAACCTTCTG 1703 CCGAACACTCTTGG 1704CCTCAACTGCAGCCTTATCCTTTTACCCATGTGCCGAAC TATCC TGAT CTTACCTCCGACTCTTGGCTTACCTCCGAGGATCACAGAAGGTTC NPBWR1 NM_005285 1705 TCACCAACCTGTT1706 GATGTTGATGGGCAG 1707 ATCGCCGACGAGCT 1708TCACCAACCTGTTCATCCTCAACCTGGCCATCGCCGA CTTCAC NPM1 NM_002520 1709AATGTTGTCCAGGTT 1710 CAAGCAAAGGGTGGAG 1711 AACAGGCATTTTGG 1712AATGTTGTCCAGGTTCTATTGCCAAGAATGTGTTGTCCA CTATTGC TTC ACAACACATTCTTGAAATGCCTGTTTAGTTTTTAAAGATGGAACTCCAC NRG1 NM_013957 1713 CGAGACTCTCCTCATAGTGAAAGGTA 1714 CTTGGCGTGTGGAAAT 1715 ATGACCACCCCGGC 1716CGAGACTCTCCTCATAGTGAAAGGTATGTGTCAGCCATG CTACAG TCGTATGTCAACCACCCCGGCTCGTATGTCACCTGTAGATTTCC NRIP3 NM_020645 1717 CCCACAAGCATGA1718 TGCTCAATCTGGCCC 1719 AGCTTTCTCTACCC 1720CCCACAAGCATGAAGGAGAAAAGCTTTCTCTACCCC CGGCAT NRP1 NM_003873 1721CAGCTCTCTCCACGC 1722 CCCAGCAGCTCCATTC 1723 CAGGATCTACCCCG 1724CAGCTCTCTCCACGCGATTCATCAGGATCTACCCCGAGA GATTC TGA AGAGAGCCACTCATGAGCCACTCATGGCGGACTGGGGCTCAGAATGGA NUP62 NM_153719 1725 AGCCTCTTTGCGTCA1726 CTGTGGTCACAGGGGT 1727 TCATCTGCCACCAC 1728AGCCTCTTTGCGTCAATAGCAACTGCTCCAACCTCATCT ATAGC ACAG TGGACTCTCCGCCACCACTGGACTCTCCCTCTGTACCCCTGTGAC OAZ1 NM_004152 1729 AGCAAGGACAGCT1730 GAAGACATGGTCGGC 1731 CTGCTCCTCAGCGA 1732AGCAAGGACAGCTTTGCAGTTCTCCTGGAGTTCGCTG ACTCCA OCLN NM_002538 1733CCCTCCCATCCGA 1734 GACGCGGGAGTGTAG 1735 CTCCTCCCTCGGTG 1736CCCTCCCATCCGAGTTTCAGGTGAATTGGTCACCGAG ACCAAT ODC1 NM_002539 1737AGAGATCACCGGCGT 1738 CGGGCTCAGCTATGAT 1739 CCAGCGTTGGACAA 1740AGAGATCACCGGCGTAATCAACCCAGCGTTGGACAAATA AATCAA TCTCA ATACTTTCCGTCACTTTCCGTCAGACTCTGGAGTGAGAATCATAGCT OLFML2 NM_015441 1741 CATGTTGGAAGGA1742 CACCAGTTTGGTGGT 1743 TGGCCTGGATCTCC 1744CATGTTGGAAGGAGCGTTCTATGGCCTGGATCTCCTG TGAAGC OLFML3 NM_020190 1745TCAGAACTGAGGC 1746 CCAGATAGTCTACCT 1747 CAGACGATCCACTC 1748TCAGAACTGAGGCCGACACCATCTCCGGGAGAGTGG TCCCGG OMD NM_005014 1749CGCAAACTCAAGACT 1750 CAGTCACAGCCTCAAT 1751 TCCGATGCACATTC 1752CGCAAACTCAAGACTATCCCAAATATTCCGATGCACATT ATCCCA TTCATT AGCAACTCTACCCAGCAACTCTACCTTCAGTTCAATGAAATTGAGG OR51E1 NM_152430 1753 GCATGCTTTCAGG1754 AGAAGATGGCCAGCA 1755 TCCTCATCTCCACC 1756GCATGCTTTCAGGCATTGACATCCTCATCTCCACCTC TCATCC OR51E2 NM_030774 1757TATGGTGCCAAAA 1758 GTCCTTGTCACAGCT 1759 ACATAGCCAGCACC 1760TATGGTGCCAAAACCAAACAGATCAGAACACGGGTG CGTGTT OSM NM_020530 1761GTTTCTGAAGGGG 1762 AGGTGTCTGGTTTGG 1763 CTGAGCTGGCCTCC 1764GTTTCTGAAGGGGAGGTCACAGCCTGAGCTGGCCTC TATGCC PAGE1 NM_003785 1765CAACCTGACGAAGTG 1766 CAGATGCTCCCTCATC 1767 CCAACTCAAAGTCA 1768CAACCTGACGAAGTGGAATCACCAACTCAAAGTCAGGAT GAATC CTCT GGATTCTACACCTGTCTACACCTGCTGAAGAGAGAGAGGATGAGGGA C PAGE4 NM_007003 1769 GAATCTCAGCAAGAG1770 GTTCTTCGATCGGAGG 1771 CCAACTGACAATCA 1772GAATCTCAGCAAGAGGAACCACCAACTGACAATCAGGAT GAACCA TGTT GGATATTGAACCTGATTGAACCTGGACAAGAGAGAGAAGGAACACCT G PAK6 NM_020168 1773 CCTCCAGGTCACC1774 GTCCCTTCAGGCCAG 1775 AGTTTCAGGAAGGC 1776CCTCCAGGTCACCCACAGCCAGTTTCAGGAAGGCTG TGCCCC PATE1 NM_138294 1777TGGTAATCCCTGG 1778 TCCACCTTATGCCTTT 1779 CAGCACAGTTCTTT 1780TGGTAATCCCTGGTTAACCTTCATGGGCTGCCTAAAG AGGCAG PAC3 NM_015342 1781CGTGATTGTCAGG 1782 AGAAAGGGGAGATGC 1783 CTGAGATGCTCCCT 1784CGTGATTGTCAGGAGCAAGACCTGAGATGCTCCCTG GCCTTC PCDHGB NM_018927 1785CCCAGCGTTGAAG 1786 GAAACGCCAGTCCGT 1787 ATTCTTAAACAGCA 1788CCCAGCGTTGAAGCAGATAAGAAGATTCTTAAACAG AGCCCC PCNA NM_002592 1789GAAGGTGTTGGAG 1790 GGTTTACACCGCTGG 1791 ATCCCAGCAGGCCT 1792GAAGGTGTTGGAGGCACTCAAGGACCTCATCAACGA CGTTGA PDE9A NM_001001570 1793TTCCACAACTTCCGG 1794 AGACTGCAGAGCCAGA 1795 TACATCATCTGGGC 1796TTCCACAACTTCCGGCACTGCTTCTGCGTGGCCCAGATG CAC CCA CACGCAGAAGATGTACAGCATGGTCTGGCTCTGCAGTCT PDGFRB NM_002609 1797 CCAGCTCTCCTTCC 1798GGGTGGCTCTCACTT 1799 ATCAATGTCCCTGT 1800CCAGCTCTCCTTCCAGCTACAGATCAATGTCCCTGTC CCGAGT PECAM1 NM_000442 1801TGTATTTCAAGACCT 1802 TTAGCCTGAGGAATTG 1803 TTTATGAACCTGCC 1804TGTATTTCAAGACCTCTGTGCACTTATTTATGAACCTGC CTGTGCACTT CTGTGTT CTGCTCCCACACCTGCTCCCACAGAACACAGCAATTCCTCAGGCT PEX10 NM_153818 1805 GGAGAAGTTCCCTCC1806 ATCTGTGTCCAGGCCC 1807 CTACCTTCGGCACT 1808GGAGAAGTTCCCTCCCCAGAAGCTCATCTACCTTCGGCA CCAG AC ACCGCTGAGCCTACCGCTGAGCCGGCGCCCGGGTGGGCCTGGAC PGD NM_002631 1809 ATTCCCATGCCCT 1810CTGGCTGGAAGCATC 1811 ACTGCCCTCTCCTT 1812ATTCCCATGCCCTGTTTTACCACTGCCCTCTCCTTCT CTATGA PGF NM_002632 1813GTGGTTTTCCCTCG 1814 AGCAAGGGAACAGCC 1815 ATCTTCTCAGACGT 1816GTGGTTTTCCCTCGGAGCCCCCTGGCTCGGGACGTCT CCCGAG PGK1 NM_000291 1817AGAGCCAGTTGCTGT 1818 CTGGGCCTACACAGTC 1819 TCTCTGCTGGGCAA 1820AGAGCCAGTTGCTGTAGAACTCAAATCTCTGCTGGGCAA AGAACTCAA CTTCA GGATGTTCTGTTCGGATGTTCTGTTCTTGAAGGACTGTGTAGGCCCA PGR NM_000926 1821 GATAAAGGAGCCG 1822TCACAAGTCCGGCAC 1823 TAAATTGCCGTCGC 1824GATAAAGGAGCCGCGTGTCACTAAATTGCCGTCGCA AGCCGC PHTF2 NM_020432 1825GATATGGCTGATG 1826 GGTTTGGGTGTTCTTG 1827 ACAATCTGGCAATG 1828GATATGGCTGATGCTGCTCCTGGGAACTGTGCATTGC CACAGT PIK3C2A NM_002645 1829ATACCAATCACCGCA 1830 CACACTAGCATTTCTC 1831 TGTGCTGTGACTGG 1832ATACCAATCACCGCACAAACCCAGGCTATTTGTTAAGTC CAAACC CGCATA ACTTAACAAATAGCCAGTCACAGCACAAAGAAACATATGCGGAGAAAA CT PIK3CA NM_006218 1833GTGATTGAAGAGC 1834 GTCCTGCGTGGGAAT 1835 TCCTGCTTCTCGGG 1836GTGATTGAAGAGCATGCCAATTGGTCTGTATCCCGA ATACAG PIK3CG NM_002649 1837GGAGAACTCAATG 1838 TGATGCTTAGGCAGG 1839 TTCTGGACAATTAC 1840GGAGAACTCAATGTCCATCTCCATTCTTCTGGACAAT TGCCAC PIM1 NM_002648 1841CTGCTCAAGGACA 1842 GGATCCACTCTGGAG 1843 TACACTCGGGTCCC 1844CTGCTCAAGGACACCGTCTACACGGACTTCGATGGG ATCGAA PLA2G7 NM_005084 1845CCTGGCTGTGGTT 1846 TGACCCATGCTGATG 1847 TGGCAATACATAAA 1848CCTGGCTGTGGTTTATCCTTTTGACTGGCAATACATA TCCTGT PLAU NM_002658 1849GTGGATGTGCCCT 1850 CTGCGGATCCAGGGT 1851 AAGCCAGGCGTCTA 1852GTGGATGTGCCCTGAAGGACAAGCCAGGCGTCTACA CACGAG PLAUR NM_002659 1853CCCATGGATGCTC 1854 CCGGTGGCTACCAGA 1855 CATTGACTGCCGAG 1856CCCATGGATGCTCCTCTGAAGAGACTTTCCTCATTGA GCCCCA PLG NM_000301 1857GGCAAAATTTCCA 1858 ATGTATCCATGAGCG 1859 TGCCAGGCCTGGGA 1860GGCAAAATTTCCAAGACCATGTCTGGACTGGAATGC CTCTCA PLK1 NM_005030 1861AATGAATACAGTATT 1862 TGTCTGAAGCATCTTC 1863 AACCCCGTGGCCGC 1864AATGAATACAGTATTCCCAAGCACATCAACCCCGTGGCC CCCAAGCACAT TGGATGA CTCCGCCTCCCTCATCCAGAAGATGCTTCAGACA PLOD2 NM_000935 1865 CAGGGAGGTGGTTGC 1866TCTCCCAGGATGCATG 1867 TCCAGCCTTTTCGT 1868CAGGGAGGTGGTTGCAAATTTCTAAGGTACAATTGCTCT AAAT AAG GGTGACTCAAATTGAGTCACCACGAAAAGGCTGGAGCTTCATG PLP2 NM_002668 1869 CCTGATCTGCTTCA1870 GCAGCAAGGATCATC 1871 ACACCAGGCTACTC 1872CCTGATCTGCTTCAGTGCCTCCACACCAGGCTACTCC CTCCCT PNLIPRP NM_005396 1873TGGAGAAGGTGAA 1874 CACGGCTTGGGTGTA 1875 ACCCGTGCCTCCAG 1876TGGAGAAGGTGAACTGCATCTGTGTGGACTGGAGGC TCCACA POSTN NM_006475 1877GTGGCCCAATTAG 1878 TCACAGGTGCCAGCA 1879 TTCTCCATCTGGCC 1880GTGGCCCAATTAGGCTTGGCATCTGCTCTGAGGCCA TCAGAG PPAP2B NM_003713 1881ACAAGCACCATCC 1882 CACGAAGAAAACTAT 1883 ACCAGGGCTCCTTG 1884ACAAGCACCATCCCAGTGATGTTCTGGCAGGATTTGC AGCAAA PPFIA3 NM_003660 1885CCTGGAGCTCCGT 1886 AGCCACATAGGGATC 1887 CACCCACTTTACCT 1888CCTGGAGCTCCGTTACTCTCAGGCACCCACTTTACCT TCTGGT PP1R12A NM_002480 1889CGGCAAGGGGTTGAT 1890 TGCCTGGCATCTCTAA 1891 CCGTTCTTCTTCCT 1892CGGCAAGGGGTTGATATAGAAGCAGCTCGAAAGGAAGAA ATAGA GCA TTCGAGCTGCGAACGGATCATGCTTAGAGATGCCAGGCA PPP3CA NM_000944 1893 ATACTCCGAGCCC 1894GGAAGCCTGTTGTTT 1895 TACATGCGGTACCC 1896ATACTCCGAGCCCACGAAGCCCAAGATGCAGGGTAC TGCATC PRIMA1 NM_178013 1897ATCCTCTTCCCTGA 1898 CCCAGCTGAGAGGGA 1899 TGACGCATCCAGGG 1900ATCCTCTTCCCTGAGCCGCTGACGCATCCAGGGCTCT CTCTAG PRKAR1 NM_002735 1901ACAAAACCATGAC 1902 TGTCATCCAGGTGAG 1903 AAGGCCATCTCCAA 1904ACAAAACCATGACTGCGCTGGCCAAGGCCATCTCCA GAACGT PRKAR2B NM_002736 1905TGATAATCGTGGGAG 1906 GCACCAGGAGAGGTAG 1907 CGAACTGGCCTTAA 1908TGATAATCGTGGGAGTTTCGGCGAACTGGCCTTAATGTA TTTCG CAGT TGTACAATACACCCCAATACACCCAGAGCAGCTACAATCACTGCTAC A PRKCA NM_002737 1909 CAAGCAATGCGTC1910 GTAAATCCGCCCCCT 1911 CAGCCTCTGCGGAA 1912CAAGCAATGCGTCATCAATGTCCCCAGCCTCTGCGG TGGATC PRKCB NM_002738 1913GACCCAGCTCCAC 1914 CCCATTCACGTACTCC 1915 CCAGACCATGGGAC 1916GACCCAGCTCCACTCCTGCTTCCAGACCATGGACCGC CGCCTGT PROM1 NM_006017 1917CTATGACAGGCAT 1918 CTCCAACCATGAGGA 1919 ACCCGAGGCTGTGT 1920CTATGACAGGCATGCCACCCCGACCACCCGAGGCTG CTCCAA PROS1 NM_000313 1921GCAGCACAGGAAT 1922 CCCACCTATCCAACCT 1923 CTCATCCTGACAGA 1924GCAGCACAGGAATCTTCTTCTTGGCAGCTGCAGTCTG CTGCAG PSCA NM_005672 1925ACCGTCATCAGCAAA 1926 CGTGATGTTCTTCTTG 1927 CCTGTGAGTCATCC 1928ACCGTCATCAGCAAAGGCTGCAGCTTGAACTGCGTGGAT GGCT CCC ACGCAGTTCAGACTCACAGGACTACTACGTGGGCAAGAAGAAC PSMD13 NM_002817 1929 GGAGGAGCTCTACAC1930 CGGATCCTGCACAAAA 1931 CCTGAAGTGTCAGC 1932GGAGGAGCTCTACACGAAGAAGTTGTGGCATCAGCTGAC GAAGAAG TCA TGATGCCACAACTTCAGGTGCTTGATTTTGTGCAGGATCCG PTCH1 NM_000264 1933 CCACGACAAAGCC 1934TACTCGATGGGCTCT 1935 CCTGAAACAAGGCT 1936CCACGACAAAGCCGACTACATGCCTGAAACAAGGCT GAGAAT PTEN NM_000314 1937TGGCTAAGTGAAGAT 1938 TGCACATATCATTAC 1939 CCTTTCCAGCTTTA 1940TGGCTAAGTGAAGATGACAATCATGTTGCAGCAATTCAC GACAATCATG ACCAGTTCGTCAGTGAATTGCTGC TGTAAAGCTGGAAAGGGACGAACTGGTGTAATG A PTGER3 NM_000957 1941TAACTGGGGCAAC 1942 TTGCAGGAAAAGGTG 1943 CCTTTGCCTTCCTG 1944TAACTGGGGCAACTTTTCTTCGCCTCTGCCTTTGCC GGGCTC PTGS2 NM_000963 1945GAATCATTCACCAGG 1946 CTGTACTGCGGGTGGA 1947 CCTACCACCAGCAA 1948GAATCATTCACCAGGCAAATTGCTGGCAGGGTTGCTGGT CAAATTG ACAT CCCTGCCAGGTAGGAATGTTCCACCCGCAGTACAG PTH1R NM_000316 1949 CGAGGTACAAGCTGA 1950GCGTGCCTTTCGCTTG 1951 CCAGTGCCAGTGTC 1952CGAGGTACAAGCTGAGATCAAGAAATCTTGGAGCCGCTG GATCAAGAA AA CAGCGGCTGACACTGGCACTGGACTTCAAGCGAAAGGCACG PTHLH NM_002820 1953 AGTGACTGGGAGTGG1954 AAGCCTGTTACCGTGA 1955 TGACACCTCCACAA 1956AGTGACTGGGAGTGGGCTAGAAGGGGACCACCTGTCTGA GCTAGAA ATCGA CGTCGCTGGACACCTCCACAACGTCGCTGGAGCTCGATTCACG PTK2 NM_005607 1957 GACCGGTCGAATG 1958CTGGACATCTCGATG 1959 ACCAGGCCCGTCAC 1960GACCGGTCGAATGATAAGGTGTACGAGAATGTGACG ATTCTC PTK2B NM_004103 1961CAAGCCCAGCCGA 1962 GAACCTGGAACTGCA 1963 CTCCGCAAACCAAC 1964CAAGCCCAGCCGACCTAAGTACAGACCCCCTCCGCA CTCCTG PTK6 NM_005975 1965GTGCAGGAAAGGTTC 1966 GCACACACGATGGAGT 1967 AGTGTCTGCGTCCA 1968GTGCAGGAAAGGTTCACAAATGTGGAGTGTCTGCGTCCA ACAAA AAGG ATACACGCGTATACACGCGTGTGCTCCTCTCCTTACTCCATCGT PTK7 NM_002821 1969 TCAGAGGACTCAC1970 CATACACCTCCACGC 1971 CGCAAGGTCCCATT 1972TCAGAGGACTCACGGTTCGAGGTCTTCAAGAATGGG CTTGAA PTPN1 NM_002827 1973AATGAGGAAGTTT 1974 CTTCGATCACAGCCA 1975 CTGATCCAGACAGC 1976AATGAGGAAGTTTCGGATGGGGCTGATCCAGACAGC CGACCA PTPRK NM_002844 1977TCAAACCCTCCCA 1978 AGCAGCCAGTTCGTC 1979 CCCCATCGTTGTAC 1980TCAAACCCTCCCAGTGCTGGCCCCATCGTTGTACATT ATTGCA PTTG1 NM_004219 1981GGCTACTCTGATCTA 1982 GCTTCAGCCCATCCTT 1983 CACACGGGTGCCTG 1984GGCTACTCTGATCTATGTTGATAAGGAAAATGGAGAACC TGTTGATAAGG AGCA GTTCTCCAAGGCACCCGTGTGGTTGCTAAGGATGGGCTGAA PYCARD NM_013258 1985 CTTTATAGACCAG1986 AGCATCCAGCAGCCA 1987 ACGTTTGTGACCCT 1988CTTTATAGACCAGCACCGGGCTGCGCTTATCGGCGAG CGCGAT RAB27A NM_004580 1989TGAGAGATTAATG 1990 CCGGATGCTTTATTCG 1991 ACAAATTGCTTCTC 1992TGAGAGATTAATGGGCATTGTGTACAAATTGCTTCTC ACCATC RAB30 NM_014488 1993TAAAGGCTGAGGC 1994 CTCCCCAGCATCTCAT 1995 CCATCAGGGCAGTT 1996TAAAGGCTGAGGCACGGAGAAGAAAAGGAATCAGCA GCTGAT RAB31 NM_006868 1997CTGAAGGACCCTA 1998 ATGCAAAGCCAGTGT 1999 CTTCTCAAAGTGAG 2000CTGAAGGACCCTACGCTCGGTGGCCTGGCACCTCAC GTGCCA RAD21 NM_006265 2001TAGGGATGGTATCTG 2002 TCGCGTACACCTCTGC 2003 CACTTAAAACGAAT 2004TAGGGATGGTATCTGAAACAACAATGGTCACCCTCTTGA AAACAACA TC CTCAAGAGGGTGACGATTCGTTTTAAGTGTAATTCCATAATGAGCAGAG CA RAD51 NM_002875 2005AGACTACTCGGGT 2006 AGCATCCGCAGAAAC 2007 CTTTCAGCCAGGCA 2008AGACTACTCGGGTCGAGGTGAGCTTTCAGCCAGGCA GATGCA RAD9A NM_004584 2009GCCATCTTCACCA 2010 CGGTGTCTGAGAGTG 2011 CTTTGCTGGACGGC 2012GCCATCTTCACCATCAAGGACTCTTTGCTGGACGGCC CACTTT RAF1 NM_002880 2013CGTCGTATGCGAG 2014 TGAAGGCGTGAGGTG 2015 TCCAGGATGCCTGT 2016CGTCGTATGCGAGAGTCTGTTTCCAGGATGCCTGTTA TAGTTC RAGE NM_014226 2017ATTAGGGGGACTTT 2018 GGGTGGAGATGTATT 2019 CCGGAGTGTCTATT 2020ATTAGGGGACTTTGGCTCCTGCCGGAGTGTCTATTCC CCAAGC RALA NM_005402 2021TGGTCCTGAATGT 2022 CCCCATTTCACCTCTT 2023 TTGTGTTTCTTGGG 2024TGGTCCTGAATGTAGCGTGTAAGCTTGTGTTTCTTGG CAGTCT RALBP1 NM_006788 2025GGTGTCAGATATAAA 2026 TTCGATATTGCCAGCA 2027 TGCTGTCCTGTCGG 2028GGTGTCAGATATAAATGTGCAAATGCCTTCTTGCTGTCC TGTGCAAATGC GCTATAAATCTCAGTACGTTCA TGTCGGTCTCAGTACGTTCACTTTATAGCTGCTGG RAP1B NM_0010109422029 TGACAGCGTGAGAGG 2030 CTGAGCCAAGAACGAC 2031 CACGCATGATGCAA 2032TGACAGCGTGAGAGGTACTAGGTTTTGACAAGCTTGCAT TACTAGG TAGCTT GCTTGTCAAACATGCGTGAGTATAAGCTAGTCGTTCTTGGCTCA RARB NM_000965 2033 ATGAACCCTTGACCC2034 GAGCTGGGTGAGATGC 2035 TGTGCTCTGCTGTG 2036ATGAACCCTTGACCCCAAGTTCAAGTGGGAACACAGCAG CAAGT TAGG TTCCCACTTGAGCACAGTCCTAGCATCTCACCCAGCTC RASSF1 NM_007182 2037 AGGGCACGTGAAGTC 2038AAAGAGTGCAAACTTG 2039 CACCACCAAGAACT 2040AGGGCACGTGAAGTCATTGAGGCCCTGCTGCGAAAGTTC ATTG CGG TTCGCAGCAGTTGGTGGTGGATGACCCCCGCAAGTTTGCACTCT RB1 NM_000321 2041 CGAAGCCCTTACA 2042GGACTCTTCAGGGGT 2043 CCCTTACGGATTCC 2044CGAAGCCCTTACAAGTTTCCTAGTTCACCCTTACGGA TGGAGG RECK NM_021111 2045GTCGCCGAGTGTG 2046 GTGGGATGATGGGTT 2047 TCAAGTGTCCTTCG 2048GTCGCCGAGTGTGCTTCTGTCAAGTGTCCTTCGCTCT CTCTTG REG4 NM_032044 2049TGCTAACTCCTGCAC 2050 TGCTAGGTTTCCCCTC 2051 TCCTCTTCCTTTCT 2052TGCTAACTCCTGCACAGCCCCGTCCTCTTCCTTTCTGCT AGCC TGAA GCTAGCCTGGCAGCCTGGCTAAATCTGCTCATTATTTCAGAGGGGA RELA NM_021975 2053 CTGCCGGGATGGC2054 CCAGGTTCTGGAAAC 2055 CTGAGCTCTGCCCG 2056CTGCCGGGATGGCTTCTATGAGGCTGAGCTCTGCCC GACCGC RFX1 NM_002918 2057TCCTCTCCAAGTTC 2058 CAGGCCCTGGTACAG 2059 TCCAATGGACCAAG 2060TCCTCTCCAAGTTCGAGCCCGTGCTCCAATGGACCAA CACTGT RGS10 NM_001005339 2061AGACATCCACGACAG 2062 CCATTTGGCTGTGCTC 2063 AGTTCCAGCAGCAG 2064AGACATCCACGACAGCGATGGCAGTTCCAGCAGCAGCCA CGAT TTG CCACCAGAGCCAGAGCCTCAAGAGCACAGCCAAATGG RGS7 NM_002924 2065 CAGGCTGCAGAGAGC 2066TTTGCTTGTGCTTCTG 2067 TGAAAATGAACTCC 2068CAGGCTGCAGAGAGCATTTGCCCGGAAGTGGGAGTTCAT ATTT CTTG CACTTCCGGGTTTCATGCAAGCAGAAGCACAAGCAAA RHOA NM_001664 2069 TGGCATAGCTCTG 2070TGCCACAGCTGCATG 2071 AAATGGGCTCAACC 2072TGGCATAGCTCTGGGGTGGGCAGTTTTTTGAAAATG AGAAA RHOB NM_004040 2073AAGCATGAACAGG 2074 CCTCCCCAAGTCAGT 2075 CTTTCCAACCCCTG 2076AAGCATGAACAGGACTTGACCATCTTTCCAACCCCTG GGGAAG RHOC NM_175744 2077CCCGTTCGGTCTG 2078 GAGCACTCAAGGTAG 2079 TCCGGTTCGCCATG 2080CCCGTTCGGTCTGAGGAAGGCCGGGACATGGCGAAC TCCCG RLN1 NM_006911 2081AGCTGAAGGCAGCCC 2082 TTGGAATCCTTTAATG 2083 TGAGAGGCAACCAT 2084AGCTGAAGGCAGCCCTATCTGAGAGGCAACCATCATTAC TATC CAGGT CATTACCAGAGCCAGAGCTACAGCAGTATGTACCTGCATTAAAGG RND3 NM_005168 2085 TCGGAATTGGACT 2086CTGGTTACTCCCCTCC 2087 TTTTAAGCCTGACT 2088TCGGAATTGGACTTGGGAGGCGCGGTGAGGAGTCAG CCTCAC RNF114 NM_018683 2089TGACAGGGGAAGT 2090 GGAAGACAGCTTTGG 2091 CCAGGTCAGCCCTT 2092TGACAGGGGAAGTGGGTCCCCAGGTCAGCCCCTTCTC CTCTTC ROBO2 NM_002942 2093CTACAAGGCCCAG 2094 CACCAGTGGCTTTAC 2095 CTGTACCATCCACT 2096CTACAAGGCCCAGCCAACCAAACGCTGGCAGTGGAT GCCAGC RRM1 NM_001033 2097GGGCTACTGGCAG 2098 CTCTCAGCATCGGTA 2099 CATTGGAATTGCCA 2100GGGCTACTGGCAGCTACATTGCTGGGACTAATGGCA TTAGTC RRM2 NM_001034 2101CAGCGGGATTAAA 2102 ATCTGCGTTGAAGCA 2103 CCAGCACAGCCAGT 2104CAGCGGGATTAAACAGTCCTTTAACCAGCACAGCCA TAAAAG S100P NM_005980 2105AGACAAGGATGCC 2106 GAAGTCCACCTGGGC 2107 TTGCTCAAGGACCT 2108AGACAAGGATGCCGTGGATAAATTGCTCAAGGACCT GGACGC SAT1 NM_002970 2109CCTTTTACCACTGC 2110 ACAATGCTGTGTCCTT 2111 TCCAGTGCTCTTTC 2112CCTTTTACCACTGCCTGGTTGCGAAGTGCCGAAAGA GGCACT SCUBE2 NM_020974 2113TGACAATCAGCACAC 2114 TGTGACTACAGCCGTG 2115 CAGGCCCTCTTCCG 2116TGACAATCAGCACACCTGCATTCACCGCTCGGAAGAGGG CTGCAT ATCCTTA AGCGGTCCTGAGCTGCATGAATAAGGATCACGGCTGTAG SDC1 NM_002997 2117 GAAATTGACGAGG 2118AGGAGCTAACGGAGA 2119 CTCTGAGCGCCTCC 2120GAAATTGACGAGGGGTGTCTTGGGCAGAGCTGGCTC ATCCAA SDC2 NM_002998 2121GGATTGAAGTGGC 2122 ACCAGCCACAGTACC 2123 AACTCCATCTCCTT 2124GGATTGAAGTGGCTGGAAAGAGTGATGCCTGGGGAA CCCCAG SDHC NM_003001 2125CTTCCCTCGGGTCT 2126 TTCCCTCCTGGTAAA 2127 TTACATCCTCCCTC 2128CTTCCCTCGGGTCTCAGGCATTTACATCCTCCCTCTC TCCCCG SEC14L1 NM_001039573 2129AGGGTTCCCATGTGA 2130 GCAGGCATGCTGTGGA 2131 CGGGCTTCTACATC 2132AGGGTTCCCATGTGACCAGGTGGCCGGGCTTCTACATCC CCAG AT CTGCAGTGGTGCAGTGGAAATTCCACAGCATGCCTGC SEC23A NM_006364 2133 CGTGTGCATTAGA 2134CCCATTACCATGTATC 2135 TCCTGGAGATGAAA 2136CGTGTGCATTAGATCAGACAGGTCTCCTGGAGATGA TGCTGT SEMA3A NM_006080 2137TTGGAATGCAGTC 2138 CTCTTCATTTCGCCTC 2139 TTGCCAATAGACCA 2140TTGGAATGCAGTCCGAAGTCGCAGAGAGCGCTGGTC GCGCTC SEPT9 NM_006640 2141CAGTGACCACGAG 2142 CTTCGATGGTACCCC 2143 TTGCCAATAGACCA 2144CAGTGACCACGAGTACCAGGTCAACGGCAAGAGGAT GCGCTC SERPINA3 NM_001085 2145GTGTGGCCCTGTCTG 2146 CCCTGTGCATGTGAGA 2147 AGGGAATCGCTGTC 2148GTGTGGCCCTGTCTGCTTATCCTTGGAAGGTGACAGCGA CTTA GCTAC ACCTTCCAAGTTCCCTGTGTAGCTCTCACATGCACAGGG SERPINB5 NM_002639 2149 CAGATGGCCACTTTG2150 GGCAGCATTAACCACA 2151 AGCTGACAACAGTG 2152CAGATGGCCACTTTGAGAACATTTTAGCTGACAACAGTG AGAACATT AGGATT TGAACGACCAGACCTGAACGACCAGACCAAAATCCTTGTGGTTAATG SESN3 NM_144665 2153 GACCCTGGTTTTG2154 GAGCTCGGAATGTTG 2155 TGCTCTTCTCCTCG 2156GACCCTGGTTTTGGGTATGAAGACTTTGCCAGACGA TCTGGC SFRP4 NM_003014 2157TACAGGATGAGGC 2158 GTTGTTAGGGCAAGG 2159 CCTGGGACAGCCTA 2160TACAGGATGAGGCTGGGCATTGCCTGGGACAGCCTA TGTAAG SH3RF2 NM_152550 2161CCATCACAACAGCCT 2162 CACTGGGGTGCTGATC 2163 AACCGGATGGTCCA 2164CCATACAACAGCCTTGAACACTCTCAACCGGATGGTCCA TGAAC TCTA TTCTCCTTCATTCTCCTTCAGGGCGCCATATGGTAGAGATCAG SH3YL1 NM_015677 2165 CCTCCAAAGCCAT2166 CTTTGAGAGCCAGAG 2167 CACAGCAGTCATCT 2168CCTCCAAAGCCATTGTCAAGACCACAGCAGTCATCT GCACCA SHH NM_000193 2169GTCCAAGGCACAT 2170 GAAGCAGCCTCCCGA 2171 CACCGAGTTCTCTG 2172GTCCAAGGCACATATCCACTGCTCGGTGAAAGCAGA CTTTCA SHMT2 NM_005412 2173AGCGGGTGCTAGA 2174 ATGGCACTTCGGTCT 2175 CCATCACTGCCAAC 2176AGCGGGTGCTAGAGCTTGTATCCATCACTGCCAACA AAGAAC SIM2 NM_005069 2177GATGGTAGGAAGG 2178 CACAAGGAGCTGTGA 2179 CGCCTCTCCACGCA 2180GATGGTAGGAAGGGATGTGCCCGCCTCTCCACGCAC CTCAGC SIPA1L1 NM_015556 2181CTAGGACAGCTTG 2182 CATAACCGTAGGGCT 2183 CGCCACAATGCCCT 2184CTAGGACAGCTTGGCTTCCATGTCAACTATGAGGGC CATAGT SKIL NM_005414 2185AGAGGCTGAATAT 2186 CTATCGGCCTCAGCA 2187 CCAATCTCTGCCTC 2188AGAGGCTGAATATGCAGGACAGTTGGCAGAACTGAG AGTTCT SLC22A3 NM_021977 2189ATCGTCAGCGAGT 2190 CAGGATGGCTTGGGT 2191 CAGCATCCACGCAT 2192ATCGTCAGCGAGTTTGACCTTGTCTGTGTCAATGCGT TGACAC SLC25A21 NM_030631 2193AAGTGTTTTTCCCCC 2194 GGCCGATCGATAGTCT 2195 TCATGGTGCTGCAT 2196AAGTGTTTTTCCCCCTTGAGATAATGGATATTTGCTATG TTGAGAT CTCTT AGCAAATATCCACAGCACCATGAAGAAGAGAGACTATCGATCGGCC SLC44A1 NM_080546 2197 AGGACCGTAGCTG2198 ATCCCATCCCAATGC 2199 TACCATGGCTGCTG 2200AGGACCGTAGCTGCACAGACATACCATGGCTGCTGC CTCTTC SMAD4 NM_005359 2201GGACATTACTGGC 2202 ACCAATACTCAGGAG 2203 TGCATTCCAGCCTC 2204GGACATTACTGGCCTGTTCACAATGAGCTTGCATTCC CCATTT SMARCC2 NM_003075 2205TACCGACTGAACCCC 2206 GACATCACCCGCTAGG 2207 TATCTTACCTCTAC 2208TACCGACTGAACCCCCAAGAAGTATCTTACCTCTACCGC CAA TTTC CGCCTGCCGCCTGCCGCCGAAACCTAGCGGGTGATGTC SMARCD1 NM_003076 2209 CCGAGTTAGCATATC 2210CCTTTGTGCCCAGCTG 2211 CCCACCCTTGCTGT 2212CCGAGTTAGACATATCCCAGGCTCGCAGACTCAACACAG CCAGG TC GTTGAGTCTGCAAGGGTGGGAGACAGCTGGGCACAAAGG SMO NM_005631 2213 GGCATCCAGTGCC 2214CGCGATGTAGCTGTG 2215 CTTCACAGAGGCTG 2216GGCATCCAGTGCCAGAACCCGCTCTTCACAGAGGCT AGCACC SNA11 NM_005985 2217CCCAATCGGAAGC 2218 GTAGGGCTGCTGGAA 2219 TCTGGATTAGAGTC 2220CCCAATCGGAAGCCTAACTACAGCGAGCTGCAGGAC CTGCAG SNRPB2 NM_003092 2221CGTTTCCTGCTTTT 2222 AGGTAGAAGGCGCAC 2223 CCCACCTAAGGCCT 2224CGTTTCCTGCTTTTGGTTCTTACAGTAGTCGGCGTAG ACGCCG SOD1 NM_000454 2225TGAAGAGAGGCAT 2226 AATAGACACATCGGC 2227 TTTGTCAGCAGTCA 2228TGAAGAGAGGCATGTTGGAGACTTGGGCAATGTGAC CATTGC SORBS1 NM_015385 2229GCAGATGAGTGGA 2230 AGCGAGTGAAGAGGG 2231 ATTTCCATTGGCAT 2232GCAGATGAGTGGAGGCTTTCTTCCAGTGCTGATGCC CAGCAC SOX4 NM_003107 2233AGATGATCTCGGG 2234 GCGCCCTTCAGTAGG 2235 CGAGTCCAGCATCT 2236AGATGATCTCGGGAGACTGGCTCGAGTCCAGCATCT CCAACC SPARC NM_003118 2237TCTTCCCTGTACACT 2238 AGCTCGGTGTGGGAGA 2239 TGGACCAGCACCCC 2240TCTTCCCTGTACACTGGCAGTTCGGCCAGCTGGACCAGC GGCAGTTC GGTA ATTGACGGACCCCATTGACGGGTACCTCTCCCACACCGAGCT SPARCL NM_004684 2241 GGCACAGTGCAAG2242 GATTGAGCTCTCTCG 2243 ACTTCATCCCAAGC 2244GGCACAGTGCAAGTGATGACTACTTCATCCCAAGCC CAGGCC SPDEF NM_012391 2245CCATCCGCCAGTATT 2246 GGGTGCACGAACTGGT 2247 ATCATCCGGAAGCC 2248CCATCCGCCAGTATTACAAGAAGGGCATCATCCGGAAGC ACAAG AGA AGACATCTCCCAGACATCTCCCAGCGCCTCGTCTACCAGTTCGT SPINK1 NM_003122 2249 CTGCCATATGACC2250 GTTGAAAACTGCACC 2251 ACCACGTCTCTTCA 2252CTGCCATATGACCCTTCCAGTCCCAGGCTTCTGAAGA GAAGCC SPINT1 NM_003710 2253ATTCCCAGCACAG 2254 AGATGGCTACCACCA 2255 CTGTCGCAGTGTTC 2256ATTCCCAGCACAGGCTCTGTGGAGATGGCTGTCGCA CTGGTC SPP1 NM_001040058 2257TCACACATGGAAAGC 2258 GTTCAGGTCCTGGGCA 2259 TGAATGGTGCATAC 2260TCACACATGGAAAGCGAGGAGTTGAATGGTGCATACAAG GAGG AC AAGGCCATCCGCCATCCCCGTTGCCCAGGACCTGAAC SQLE NM_003219 2261 ATTTTCGAGGCCAAA 2262CCTGAGCAAGGATATT 2263 TGGGCAAGAAAAAC 2264ATTTTCGAGGCCAAAAAATCATTTACTGGGCAAGAAAAA AAATC CACG ATCTCATTCCTTTGCATCTCATTCCTTTGTCGTGAATATCCTTGCTC SRC NM_005417 2265 TGAGGAGTGGTATTT2266 CTCTCGGGTTCTCTGC 2267 AACCGCTCTGACTC 2268TGAGGAGTGGTATTTTGGCAAGATCACCAGACGGGAGTC TGGCAAGA ATTGA CCGTCTGGTGAGAGCGGTTACTGCTCAATGCAGAGAACCCGAG SRD5A1 NM_001047 2269 GGGCTGGAATCTG2270 CCATGACTGCACAAT 2771 CCTCTCTCGGAGGC 2272GGGCTGGAATCTGTCTAGGAGCCCTCTCTCGGAGGC CACAGA SRD5A2 NM_000348 2273GTAGGTCTCCTGGCG 2274 TCCCTGGAAGGGTAGG 2275 AGACACCACTCAGA 2276GTAGGTCTCCTGGCGTTCTGCCAGCTGGCCTGGGGATTC TTCTG AGTAA ATCCCCAGGCTGAGTGGTGTCTGCTTAGAGTTTACTCCTACCCTT ST5 NM_005418 2277 CCTGTCCTGCCAG2278 CAGCTGCACAAAACT 2279 AGTCACGAGCACCC 2280CCTGTCCTGCCAGAGCATGGATGAAGTTTCGCTGGGT AGCGA STAT1 NM_007315 2281GGGCTCAGCTTTCAG 2282 ACATGTTCAGCTGGTC 2283 TGGCAGTTTTCTTC 2284GGGCTCAGCTTTCAGAAGTGCTGAGTTGGCAGTTTTCTT AAGTG CACA TGTCACCAAAACTGTCACCAAAAGAGGTCTCAATGTGGACCAGCT STAT3 NM_003150 2285 TCACATGCCACTTT2286 CTTGCAGGAAGCGGC 2287 TCCTGGGAGAGATT 2288TCACATGCCACTTTGGTGTTTCATAATCTCCTGGGAG GACCAG STAT5A NM_003152 2289GAGGCGCTCAACATG 2290 GCCAGGAACACGAGGT 2291 CGGTTGCTCTGCAC 2292GAGGCGCTCAACATGAAATTCAAGGCCGAAGTGCAGAGC AAATTC TCTC TTCGGCCTAACCGGGGCCTGACCAAGGAGAACCTCGTGTTC STAT5B NM_012448 2293 CCAGTGGTGGTGA2294 GCAAAAGCATTGTCC 2295 CAGCCAGGACAACA 2296CCAGTGGTGGTGATCGTTCATGGCAGCCAGGACAAC ATGCG STMN1 NM_005563 2297AATACCCAACGCA 2298 GGAGACAATGCAAAC 2299 CACGTTCTCTGCCC 2300AATACCCAACGCACAAATGACCGCACGTTCTCTGCC CGTTTC STS NM_000351 2301GAAGATCCCTTTCCT 2302 GGATGATGTTCGGCCT 2303 CTGCGTGGCTCTCG 2304GAAGATCCCTTTCCTCCTACTGTTCTTTCTGTGGGAAGC CCTACTGTTC TGAT GCTTCCCACGAGAGCCACGCAGCATCAAGGCCGAACATCATC SULF1 NM_015170 2305 TGCAGTTGTAGGGAG2306 TCTCAAGAATTGCCGT 2307 TACCGTGCCAGCAG 2308TGCAGTTGTAGGGAGTCTGGTTACCGTGCCAGCAGAAGC TCTGG TGAC AAGCCAAAGCAAAGAAAGAGTCAACGGCAATTCTTGAGA SUMO1 NM_003352 2309 GTGAAGCCACCGT 2310CCTTCCTTCTTATCCC 2311 CTGACCAGGAGGCA 2312GTGAAGCCACCGTCATCATGTCTGACCAGGAGGCAA AAACCT SVIL NM_003174 2313ACTTGCCCAGCAC 2314 GACACCATCCGTGTC 2315 ACCCCAGGACTGAT 2316ACTTGCCCAGCACAAGGAAGACCCCAGGACTGATGT GTCAAG TAF2 NM_003184 2317GCGCTCCACTCTCAG 2318 CTTGTGCTCATGGTGA 2319 AGCCTCCAAACACA 2320GCGCTCCACTCTCAGTCTTTACTAAGGAATCTACAGCCT TCTTT TGGT GTGACCACCACCAAACACAGTGACCACCATCACCACCATCACCAT TARP NM_001003799 2321GAGCAACACGATTCT 2322 GGCACCGTTAACCAGC 2323 TCTTCATGGTGTTC 2324GAGCAACACGATTCTGGGATCCCAGGAGGGGAACACCAT GGGA TAAAT CCCTCCTGGGAAGACTAACGACACATACATGAAATTTAGCTG TBP NM_003194 2325 GCCCGAAACGCCG 2326CGTGGCTCTCTTATCC 2327 TACCGCAGCAAACC 2328GCCCGAAACGCCGAATATAATCCCAAGCGGTTTGCT GCTTGG TFDP1 NM_007111 2329TGCGAAGTGCTTTTG 2330 GCCTTCCAGACAGTCT 2331 CGCACCAGCATGGC 2332TGCGAAGTGCTTTTGTTTGTTTGTTTTCGTTTGGTTAAA TTTGT CCAT AATAAGCTTTGCTTATTGCCATGCTGGTGCGGCTATGGAGACTGTC TFF1 NM_003225 2333 GCCCTCCCAGTGTGC2334 CGTCGATGGTATTAGG 2335 TGCTGTTTCGACGA 2336GCCCTCCCAGTGTGCAAATAAGGGCTGCTGTTTCGACGA AAAT ATAGAAGCA CACCGTTCGCACCGTTCGTGGGGTCCCCTGGTGCTTCTATCCTA TFF3 NM_003226 2337 AGGCACTGTTCATCT2338 CATCAGGCTCCAGATA 2339 CAGAAGCGCTTGCC 2340AGGCACTGTTCATCTCAGCTTTTCTGTCCCTTTGCTCCC CAGTTTTTCT TGAACTTTC GGGAGCAAAGGGGCAAGCGCTTCTGCTGAAAGTTCATATCTGGAG TGFA NM_003236 2341 GGTGTGCCACAGACC2342 ACGGAGTTCTTGACAG 2343 TTGGCCTGTAATCA 2344GGTGTGCCACAGACCTTCCTACTTGGCCTGTAATCACCT TTCCT AGTTTTGA CCTGTGCAGCCTTGTGCAGCCTTTTGTGGGCCTTCAAAACTCTGTCAA TGFB1II NM_001042454 2345GCTACTTTGAGCGCT 2346 GGTCACCATCTTGTGT 2347 CAAGATGTGGCTTC 2348GCTACTTTGAGCGCTTCTCGCCAAGATGTGGCTTCTGCA TCTCG CGG TGCAACCAGCACCAGCCCATCCGACACAAGATGGTGACC TGFB2 NM_003238 2349 ACCAGTCCCCCAG 2350CCTGGTGCTGTTGTA 2351 TCCTGAGCCCGAGG 2352ACCAGTCCCCCAGAAGACTATCCTGAGCCCGAGGAA AAGTCC TGFB3 NM_003239 2353GGATCGAGCTCTT 2354 GCCACCGATATAGCG 2355 CGGCCAGATGAGCA 2356GGATCGAGCTCTTCCAGATCCTTCGGCCAGATGAGC CATTGC TGFBR2 NM_003242 2357AACACCAATGGGT 2358 CCTCTTCATCAGGCC 2359 TTCTGGGCTCCTGA 2360AACACCAATGGGTTCCATCTTTCTGGGCTCCTGATTG TTGCTC THBS2 NM_003247 2361CAAGACTGGCTACAT 2362 CAGCGTAGGTTTGGTC 2363 TGAGTCTGCCATGA 2364CAAGACTGGCTACATCAGAGTCTTAGTGCATGAAGGAAA CAGAGTCTTAG ATAGATAGGCCTGTTTTCCTTCA ACAGGTCATGGCAGACTCAGGACCTATCTATGA T THY1 NM_006288 2365GGACAAGACCCTC 2366 TTGGAGGCTGTGGGT 2367 CAAGCTCCCAAGAG 2368GGACAAGACCCTCTCAGGCTGTCCCAAGCTCCCAAG CTTCCA TIAM1 NM_003253 2369GTCCCTGGCTGAA 2370 GGGCTCCCGAAGTCT 2371 TGGAGCCCTTCTCC 2372GTCCCTGGCTGAAAATGGCCTGGAGCCCTTCTCCCAA CAAGAT TIMP2 NM_003255 2373TCACCCTCTGTGA 2374 TGTGGTTCAGGCTCTT 2375 CCCTGGGACACCCT 2376TCACCCTCTGTGACTTCATCGTGCCCTGGGACACCCT GAGCAC TIMP3 NM_000362 2377CTACCTGCCTTGCT 2378 ACCGAAATTGGAGAG 2379 CCAAGAACGAGTGT 2380CTACCTGCCTTGCTTTGTGACTTCCAAGAACGAGTGT CTCTGG TK1 NM_003258 2381GCCGGGAAGACCGTA 2382 CAGCGGCACCAGGTTC 2383 CAAATGGCTTCCTC 2384GCCGGGAAGACCGTAATTGTGGCTGCACTGGATGGGACC ATTGT AG TGGAAGGTCCCATTCCAGAGGAAGCCATTTGGGGCCATCCTGAAC TMPRSS NM_005656 2385 GGACAGTGTGCAC2386 CTCCCACGAGGAAGG 2387 AAGCACTGTGCATC 2388GGACAGTGTGCACCTCAAAGACTAAGAAAGCACTGT ACCTTG TMPRSS DQ204772 2389GAGGCGGAGGGCGAG 2390 ACTGGTCCTCACTCAC 2391 TAAGGCTTCCTGCC 2392GAGGCGGAGGCGGAGGGCGAGGGGCGGGGAGCGCCGCCT 2ERGA AACT GCGCTCCAGGAGCGCGGCAGGAAGCCTTATCAGTTGTGAG TMPRSS DQ204773 2393 GAGGCGGAGGGCGAG2394 TTCCTCGGGTCTCCAA 2395 CCTGGAATAACCTG 2396GAGGCGGAGGGCGAGGGGCGGGGAGCGCCGCCTGGAGCG 2ERGB AGAT CCGCGCCGGCAGGTTATTCCAGGATCTTTGGAGACCCG TNF NM_000594 2397 GGAGAAGGGTGAC 2398TGCCCAGACTCGGCA 2399 CGCTGAGATCAATC 2400GGAGAAGGGTGACCGACTCAGCGCTGAGATCAATCG GGCCCG TNFRSF1 NM_003844 2401TGCACAGAGGGTGTG 2402 TCTTCATCTGATTTAC 2403 CAATGCTTCCAACA 2404TGCACAGAGGGTGTGGGTTACACCAATGCTTCCAACAAT 0A GGTTAC AAGCTGTACATGATTTGTTTGCTTGC TTGTTTGCTTGCCTCCCATGTACAGCTTGTAAAT C TNFRSF1 NM_0038422405 CTCTGAGACAGTGCT 2406 CCATGAGGCCCAACTT 2407 CAGACTTGGTGCCC 2408CTCTGAGACAGTGCTTCGATGACTTTGCAGACTTGGTTG 0B TCGATGACT CCT TTTGACTCCCCCTTTGACTCCTGGGAGCCGCTCATGAGGAAGTT TNFRSF1 NM_148901 2409CAGAAGCTGCCAGTT 2410 CACCCACAGGTCTCCC 2411 CCTTCTCCTCTGCC 2412CAGAAGCTGCCAGTTCCCCGAGGAAGAGCGGGGCGAGCG 8 CCC AG GATCGCTCATCGGCAGAGGAGAAGGGGCGGCTGGGAGACCT TNFSF10 NM_003810 2413 CTTCACAGTGCTC2414 CATCTGCTTCAGCTCG 2415 AAGTACACGTAAGT 2416CTTCACAGTGCTCCTGCAGTCTCTCTGTGTGGCTGTA TACAGC TNFSF11 NM_003701 2417AACTGCATGTGGG 2418 TGACACCCTCTCCACT 2419 ACATGACCAGGGAC 2420AACTGCATGTGGGCTATGGGAGGGGTTGGTCCCTGG CAACCC TOP2A NM_001067 2421AATCCAAGGGGGA 2422 GTACAGATTTTGCCC 2423 CATATGGACTTTG 2424AATCCAAGGGGGAGAGTGATGACTTCCATATGGACT ACTCAGC TP53 NM_000546 2425CTTTGAACCCTTGC 2426 CCCGGGACAAAGCAA 2427 AAGTCCTGGGTGC 2428CTTTGAACCCTTGCTTGCAATAGGTGTGCGTCAGAAG TTCTGAC TP63 NM_003722 2429CCCCAAGCAGTGC 2430 GAATCGCACAGCATC 2431 CCCGGGTCTCACT 2432CCCCAAGCAGTGCCTCTACAGTCAGTGTGGGCTCCA GGAGCCC TPD52 NM_005079 2433GCCTGTGAGATTC 2434 ATGTGCTTGGACCTC 2435 TCTGCTACCCACT 2436GCCTGTGAGATTCCTACCTTTGTTCTGCTACCCACTG GCCAGAT TPM1 NM_001018005 2437TCTCTGAGCTCTGCA 2438 GGCTCTAAGGCAGGAT 2439 TTCTCCAGCTGAC 2440TCTCTGAGCTCTGCATTTGTCTATTCTCCAGCTGACCCT TTTGTC GCTA CCTGGTTCTCTCGGTTCTCTCTCTTAGCATCCTGCTTAGAGCC TPM2 NM_213674 2441 AGGAGATGCAGCT 2442CCACCTCTTCATATTT 2443 CCAAGCACATCGC 2444AGGAGATGCAGCTGAAGGAGGCCAAGCACATCGCTG TGAGGAT TPP2 NM_003291 2445TAACCGTGGCATC 2446 ATGCCAACGCCATGA 2447 ATCCTGTTCAGGT 2448TAACCGTGGCATCTACCTCCGAGATCCTGTTCAGGTG GGCTGCA TPX2 NM_012112 2449TCAGCTGTGAGCTGC 2450 ACGGTCCTAGGTTTGA 2451 CAGGTCCCATTGC 2452TCAGCTGTGAGCTGCGGATACCGCCCGGCAATGGGACCT GGATA GGTTAAGA CGGGCGGCTCTTAACCTCAAACCTAGGACCGT TRA2A NM_013293 2453 GCAAATCCAGATC 2454CTTCACGAAGATCCC 2455 AACTGAGGCCAAA 2456GCAAATCCAGATCCCAACACTTGCCTTGGAGTGTTTG CACTCCA TRAF31P NM_147200 2457CCTCACAGGAACC 2458 CTGGGGCTGGGAATC 2459 TGGATCTGCCAAC 2460CCTCACAGGAACCGAGCAGGCCTGGATCTGCCAACC CATAGAC TRAM1 NM_014294 2461CAAGAAAAGCACC 2462 ATGTCCGCGTGATTCT 2463 AGTGCTGAGCCAC 2464CAAGAAAAGCACCAAGAGCCCCCCAGTGCTGAGCCA GAATTCG TRAP1 NM_016292 2465TTACCAGTGGCTTT 2466 TGTCCCGGTTCTAACT 2467 TTCGGCGATTTCA 2468TTACCAGTGGCTTTCAGATGGTTCTGGAGTGTTTGAA AACACTC TRIM14 NM_033220 2469CATTCGCCTTAAG 2470 CAAGGTACCTGGCTT 2471 AACTGCCAGCTCT 2472CATTCGCCTTAAGGAAAGCATAAACTGCCAGCTCTCA CAGACCC TRO NM_177556 2473GCAACTGCCACCC 2474 TGGTGTGGATACTGG 2475 CCACCCAAGGCCAA 2476GCAACTGCCACCCATACAGCTACCACCCAAGGCCAA ATTACC TRPC6 NM_004621 2477CGAGAGCCAGGACTA 2478 TAGCCGTAGCAAGGCA 2479 CTTCTCCCAGCTCC 2480CGAGAGCCAGGACTATCTGCTCATGGACTCGGAGCTGGG TCTGC GC GAGTCCATGAGAAGACGGCTGCCCGCAAGCCCCGCTGCCTTG TRPV6 NM_018646 2481 CCGTAGTCCCTGCAA2482 TCCTCACTGTTCACAC 2483 ACTTTGGGGAGCAC 2484CCGTAGTCCCTGCAACCTCATCTACTTTGGGGAGCACCC CCTC AGGC CCTTTGTCCTTTTGTCCTTTGCTGCCTGTGTGAACAGTGAGGA TSTA3 NM_003313 2485 CAATTTGGACTTCT2486 CACCTCAAAGGCCGA 2487 AACGTGCACATGAA 2488CAATTTGGACTTCTGGAGGAAAAACGTGCACATGAA CGACAA TUBB2A NM_001069 2489CGAGGACGAGGCT 2490 ACCATGCTTGAGGAC 2491 TCTCAGATCAATCG 2492CGAGGACGAGGCTTAAAAACTTCTCAGATCAATCGT TGCATC TYMP NM_001953 2493CTATATGCAGCCAGA 2494 CCACGAGTTTCTTACT 2495 ACAGCCTGCCACTC 2496CTATATGCAGCCAGAGATGTGACAGCCACCGTGGACAGC GATGTGACA GAGAATGG ATCACAGCCCTGCCACTCATCACAGCCTCCATTCTCAGTAAGA TYMS NM_001071 2497 GCCTCGGTGTGCC2498 CGTGATGTGCGCAAT 2499 CATCGCCAGCTACG 2500GCCTCGGTGTGCCTTTCAACATCGCCAGCTACGCCCT CCCTGC UAP1 NM_003115 2501CTGGAGACGGTCGTA 2502 GCCAAGCTTTGTAGAA 2503 TACCTGTAAACCTT 2504CTGGAGACGGTCGTAGCTGCGGTCGCGCCGAGAAAGGTT GCTG ATAGGG TCTCGGCGCGTACAGGTACATACATTACACCCCTATTTCTACAA UBE2C NM_007019 2505 TGTCTGGCGATAA2506 ATGGTCCCTACCCATT 2507 TCTGCCTTCCCTGA 2508TGTCTGGCGATAAAGGGATTTCTGCCTTCCCTGAATC ATCAGA UBE2G1 NM_003342 2509TGACACTGAACGA 2510 AAGCAGAGAGGAATC 2511 TTGTCCCACCAGTG 2512TGACACTGAACGAGGTGGCTTTTGTCCCACCAGTGCC CCTCAT UBE2T NM_014176 2513TGTTCTCAAATTGC 2514 AGAGGTCAACAAGT 2515 AGGTGCTTGGAGAC 2516TGTTCTCAAATTGCCACCAAAAGGTGCTTGGAGACC CATCCC UGDH NM_003359 2617GAAACTCCAGAGG 2518 CTCTGGGAACCCAGT 2519 TATACAGCACACAG 2520GAAACTCCAGAGGGCCAGAGAGCTGTGCAGGCCCTG GGCCTG UGT2B1 NM_001076 2521AAGCCTGAAGTGG 2522 CCTCCATTTAAAACCC 2523 AAAGATGGGACTCC 2524AAGCCTGAAGTGGAATGACTGAAAGATGGGACTCCT TCCTTT UGT2B1 NM_001077 2525TTGAGTTTGTCATG 2526 TCCAGGTGAGGTTGT 2527 ACCCGAAGGTGCTT 2528TTGAGTTTGTCATGCGCCATAAAGGAGCCAAGCACC GGCTCC UHRF1 NM_013282 2529CTACAGGGGCAAA 2530 GGTGTCATTCAGGCG 2531 CGGCCATACCCTCT 2532CTACAGGGGCAAACAGATGGAGGACGGCCATACCCT TCGACT UTP23 NM_032334 2533GATTGCACAAAAA 2534 GGAAAGCAGACATTC 2535 TCGAAATTGTCCTC 2536GATTGCACAAAAATGCCAAGTTCGAAATTGTCCTCAT ATTTCA VCAM1 NM_001078 2537TGGCTTCAGGAGCTG 2538 TGCTGTCGTGATGAGA 2539 CAGGCACACACAGG 2540TGGCTTCAGGAGCTGAATACCCTCCCAGGCACACACAGG AATACC AAATAGTG TGGGACACAAATTGGGACACAAATAAGGGTTTTGGAACCACTATT VCL NM_003373 2541 GATACCACAACTCCC2542 TCCCTGTTAGGCGCAT 2543 AGTGGCAGCCACGG 2544GATACCACAACTCCCATCAAGCTGTTGGCAGTGGCAGCC ATCAAGCT CAG CGCCACGGCGCCTCCTGATGCGCCTAACAGGGA VCPIP1 NM_025054 2545 TTTCTCCCAGTACC 2546TGAATAGGGAGCCTT 2547 TGGTCCATCCTCTG 2548TTTCTCCCAGTACCATTCGTGATGGTCCATCCTCTGC CACCTG VDR NM_000376 2549CCTCTCCTTCCAGC 2550 TCATTGCCAAACACTT 2551 CAGCATGAAGCTAA 2552CCTCTCCTTCCAGCCTGAGTGCAGCATGAAGCTAACG CGCCCC VEGFA NM_003376 2553CTGCTGTCTTGGG 2554 GCAGCCTGGGACCAC 2555 TTGCCTTGCTGCTC 2556CTGCTGTCTTGGGTGCATTGGAGCCTTGCCTTGCTGC TACCTC VEGFB NM_003377 2557TGACGATGGCCTG 2558 GGTACCGGATCATGA 2559 CTGGGCAGCACCAA 2560TGACGATGGCCTGGAGTGTGTGCCCACTGGGCAGCA GTCCGG VEGFC NM_005429 2561CCTCAGCAAGACGTT 2562 AAGTGTGATTGGCAAA 2563 CCTCTCTCTCAAGG 2564CCTCAGCAAGACGTTATTTGAAATTACAGTGCCTCTCTC ATTTGAAATT ACTGATTG CCCCAAACCAGTTCAAGGCCCCAAACCAGTAACAATCAGTTTTGCCA VIM NM_003380 2565 TGCCCTTAAAGGA2566 GCTTCAACGGCAAAG 2567 ATTTCACGCATCTG 2568TGCCCTTAAAGGAACCAATGAGTCCCTGGAACGCCA GCGTTC VTI1B NM_006370 2569ACGTTATGCACCCCT 2570 CCGATGGAGTTTAGCA 2571 CGAAACCCCATGAT 2572ACGTTATGCACCCCTGTCTTTCCGAAACCCCATGATGTC GTCTT AGGT GTCTAAGCTTCGTAAGCTTCGAAACTACCGGAAGGACCTTGCTAAA WDR19 NM_025132 2573 GAGTGGCCCAGAT2574 GATGCTTGAGGGCTT 2575 CCCCTCGACGTATG 2576GAGTGGCCCAGATGTCCATAAGAATGGGAGACATAC TCTCCC WFDC1 NM_021197 2577ACCCCTGCTCTGT 2578 ATACCTTCGGCCACG 2579 CTATGAGTGCCACA 2580ACCCCTGCTCTGTCCCTCGGGCTATGAGTGCCACATC TCCTGA WISP1 NM_003882 2581AGAGGCATCCATGAA 2582 CAAACTCCACAGTACT 2583 CGGGCTGCATCAGC 2584AGAGGCATCCATGAACTTCACACTTGCGGGCTGCATCAG CTTCACA TGGGTTGA ACACGCGCACACGCTCCTATCAACCCAAGTACTGTGGAGTT WNT5A NM_003392 2585 GTATCAGGACCACAT2586 TGTCGGAATTGATACT 2587 TTGATGCCTGTCTT 2588GTATCAGGACCACATGCAGTACATCGGAGAAGGCGCGAA GCAGTACATC GGCATT CGCGCCTTCTGACAGGCATCAAAGAATGCCAGTATCAATTCCG WWOX NM_016373 2589 ATCGCAGCTGGTG 2590AGCTCCCTGTTGCAT 2591 CTGCTGTTTACCTT 2592ATCGCAGCTGGTGGGTGTACACACTGCTGTTTACCTT GGCGAG XIAP NM_001167 2593GCAGTTGGAAGACAC 2594 TGCGTGGCACTATTTT 2595 TCCCCAAATTGCAG 2596GCAGTTGGAAGACACAGGAAAGTATCCCCAAATTGCAGA AGGAAAGT CAAGA ATTTATCAACGGCTTTATCAACGGCTTTTATCTTGAAAATAGTGCCA XRCC5 NM_021141 2597 AGCCCACTTCAGC2598 AGCAGGATTCACACT 2599 TCTGGCTGAAGGCA 2600AGCCCACTTCAGCGTCTCCAGTCTGGCTGAAGGCAG GTGTCA YY1 NM_003403 2601ACCCGGGCAACAA 2602 GACCGAGAACTCGCC 2603 TTGATCTGCACCTG 2604ACCCGGGCAACAAGAAGTGGGAGCAGAAGCAGGTGC CTTCTG ZFHX3 NM_006885 2605CTGTGGAGCCTCT 2606 GGAGCAGGGTTGGAT 2607 ACCTGGCCCAACTC 2608CTGTGGAGCCTCTGCCTGCGGACCTGGCCCAACTCTA TACCAG ZFP36 NM_003407 2609CATTAACCCACTC 2610 CCCCCACCATCATGA 2611 CAGGTCCCCAAGTG 2612CATTAACCCACTCCCCTGACCTCACGCTGGGGCAGGT TGCAAG ZMYND8 NM_183047 2613GGTCTGGGCCAAA 2614 TGCCCGTCTTTATCCC 2615 CTTTTGCAGGCCAG 2616GGTCTGGGCCAAACTGAAGGGGTTTCCATTCTGGCCT AATGGA ZNF3 NM_017715 2617CGAAGGGACTCTG 2618 GCAGGAGGTCCTCAG 2619 AGGAGGTTCCACAC 2620CGAAGGGACTCTGCTCCAGTGAACTGGCGAGTGTGG TCGCCA ZNF827 NM_178835 2621TGCCTGAGGACCC 2622 GAGGTGGCGGAGTGA 2623 CCCGCCTTCAGAGA 2624TGCCTGAGGACCCTCTACCGCCCCCGCCTTCAGAGA AGAAAC ZWINT NM_007057 2625TAGAGGCCATCAA 2626 TCCGTTTCCTCTGGGC 2627 ACCAAGGCCCTGAC 2628TAGAGGCCATCAAAATTGGCCTCACCAAGGCCCTGA TCAGAT

TABLE B SEQ ID microRNA Sequence NO hsa-miR-1 UGGAAUGUAAAGAAGUAUGUAU2629 hsa-miR-103 GCAGCAUUGUACAGGGCUAUGA 2630 hsa-miR-106bUAAAGUGCUGACAGUGCAGAU 2631 hsa-miR-10a UACCCUGUAGAUCCGAAUUUGUG 2632hsa-miR-133a UUUGGUCCCCUUCAACCAGCUG 2633 hsa-miR-141UAACACUGUCUGGUAAAGAUGG 2634 hsa-miR-145 GUCCAGUUUUCCCAGGAAUCCCU 2635hsa-miR-146b-5p UGAGAACUGAAUUCCAUAGGCU 2636 hsa-miR-150UCUCCCAACCCUUGUACCAGUG 2637 hsa-miR-152 UCAGUGCAUGACAGAACUUGG 2638hsa-miR-155 UUAAUGCUAAUCGUGAUAGGGGU 2639 hsa-miR-182UUUGGCAAUGGUAGAACUCACACU 2640 hsa-miR-191 CAACGGAAUCCCAAAAGCAGCUG 2641hsa-miR-19b UG UAAACAUCCUCGACUGGAAG 2642 hsa-miR-200cUAAUACUGCCGGGUAAUGAUGGA 2643 hsa-miR-205 UCCUUCAUUCCACCGGAGUCUG 2644hsa-miR-206 UGGAAUGUAAGGAAGUGUGUGG 2645 hsa-miR-21UAGCUUAUCAGACUGAUGUUGA 2646 hsa-miR-210 CUGUGCGUGUGACAGCGGCUGA 2647hsa-miR-22 AAGCUGCCAGUUGAAGAACUGU 2648 hsa-miR-222 AGCUACAUCUGGCUACUGGGU2649 hsa-miR-26a UUCAAGUAAUCCAGGAUAGGCU 2650 hsa-miR-27aUUCACAGUGGCUAAGUUCCGC 2651 hsa-miR-27b UUCACAGUGGCUAAGUUCUGC 2652hsa-miR-29b UAGCACCAUUUGAAAUCAGUGUU 2653 hsa-miR-30aCUUUCAGUCGGAUGUUUGCAGC 2654 hsa-miR-30e-5p CUUUCAGUCGGAUGUUUACAGC 2655hsa-miR-31 AGGCAAGAUGCUGGCAUAGCU 2656 hsa-miR-331 GCCCCUGGGCCUAUCCUAGAA2657 hsa-miR-425 AAUGACACGAUCACUCCCGUUGA 2658 hsa-miR-449aUGGCAGUGUAUUGUUAGCUGGU 2659 hsa-miR-486-5p UCCUGUACUGAGCUGCCCCGAG 2660hsa-miR-92a UAUUGCACUUGUCCCGGCCUGU 2661 hsa-miR-93CAAAGUGCUGUUCGUGCAGGUAG 2662 hsa-miR-99a AACCCGUAGAUCCGAUCUUGUG 2663

1. A method for determining a likelihood of cancer recurrence in apatient with prostate cancer, comprising: measuring an expression levelof at least one gene in a biological sample comprising prostate tissueobtained from the patient, wherein the at least one gene comprises agene from Tables 3A, 3B, 4A, 4B, 5A, 5B, 6A, 6B, 7A, 7B, 8A, 8B, 10A, or10B, or genes that co-express with the at least one gene; predicting alikelihood of cancer recurrence for the patient; wherein an expressionlevel of any gene in Tables 3A, 4A, 5A, 6A, 7A, 8A, and 10A ispositively associated with an increased risk of recurrence, and whereinan expression level of any gene in Tables 3B, 4B, 5B, 6B, 7B 8B, and 10Bis negatively associated with a increased risk of recurrence.
 2. Themethod of claim 1, wherein said expression level is measured using anRNA transcript of the at least one gene.
 3. The method of claim 1,wherein said expression is measured using an oligonucleotide associatedwith the at least one gene.
 4. The method of claim 1, further comprisingnormalizing said expression level to obtain a normalized expressionlevel.
 5. The method of claim 1, further comprising generating a reportbased on the Recurrence Score (RS).
 6. The method of claim 5, whereinthe report comprises an estimate of recurrence risk based on clinicalrecurrence-free interval (cRFI).
 7. The method of claim 5, wherein theRS is based on a biochemical recurrence-free interval (bRFI).
 8. Themethod of claim 1, wherein the biological sample has a positive TMPRSS2fusion status.
 9. The method of claim 1, wherein the biological samplehas a negative TMPRSS2 fusion status.
 10. The method of claim 1, whereinthe patient has early-stage prostate cancer.
 11. The method of claim 1,wherein the biological sample comprises prostate tumor tissue with theprimary Gleason pattern for said prostate tumor.
 12. The method of claim1, wherein the biological samples comprises prostate tumor tissue withthe highest Gleason pattern for said prostate tumor.
 13. The method ofclaim 1, wherein the biological sample is prostate tumor tissue.
 14. Themethod of claim 1, wherein the biological sample is non-tumor prostatetissue.
 15. The method of claim 1, further comprising classifying thepatient as TMPRSS2 fusion positive or negative, wherein an expressionlevel of any gene in Table 9A is associated with a positive TMPRSS2fusion status, and wherein an expression level of any gene in Table 9Bis associated with a negative TMPRSS2 fusion status.
 16. The method ofclaim 1, wherein the biological sample comprises non-tumor prostatetissue, and wherein the at least one gene comprises a gene from Tables10A or 10B.
 17. A method for determining a likelihood of upgrading orupstaging in a patient with prostate cancer, comprising: measuring anexpression level of at least one gene in a biological sample comprisingprostate tissue obtained from the patient, wherein the at least one genecomprises a gene from Table 13A or 13B, or genes that co-express withthe at least one gene; wherein an expression level of any gene in Tables13A is positively associated with an increased risk ofupgrading/upstaging, and wherein an expression level of any gene inTable 13B is negatively associated with a increased risk ofupgrading/upstaging.
 18. A method for determining a likelihood of cancerrecurrence in a patient with prostate cancer, comprising: measuring anexpression level of at least one microRNA in a biological samplecomprising prostate tissue obtained from the patient, wherein the atleast one microRNA is a microRNA selected from hsa-miR-93; hsa-miR-106b;hsa-miR-21; hsa-miR-449a; hsa-miR-182; hsa-miR-27a; hsa-miR-103;hsa-miR-141; hsa-miR-92a; hsa-miR-22; hsa-miR-29b; hsa-miR-210;hsa-miR-331; hsa-miR-191; hsa-miR-425; hsa-miR-200c; hsa-miR-30e-5p;hsa-miR-133a; hsa-miR-30a; hsa-miR-222; hsa-miR-1; hsa-miR-145;hsa-miR-486-5p; hsa-miR-19b; hsa-miR-205; hsa-miR-31; hsa-miR-155;hsa-miR-206; hsa-miR-99a; and hsa-miR-146b-5p; and normalizing saidexpression level to obtain a normalized expression level; wherein anormalized expression level of hsa-miR-93; hsa-miR-106b; hsa-miR-21;hsa-miR-449a; hsa-miR-182; hsa-miR-27a; hsa-miR-103; hsa-miR-141;hsa-miR-92a; hsa-miR-22; hsa-miR-29b; hsa-miR-210; hsa-miR-331;hsa-miR-191; hsa-miR-425; and hsa-miR-200c is positively associated withan increased risk of recurrence; and wherein a normalized expressionlevel of hsa-miR-30e-5p; hsa-miR-133a; hsa-miR-30a; hsa-miR-222;hsa-miR-1; hsa-miR-145; hsa-miR-486-5p; hsa-miR-19b; hsa-miR-205;hsa-miR-31; hsa-miR-155; hsa-miR-206; hsa-miR-99a; and hsa-miR-146b-5pis negatively associated with an increased risk of recurrence.
 19. Themethod of claim 18, further comprising measuring an expression level ofat least one gene in said biological sample.
 20. The method of claim 19,wherein the at least one gene is a gene selected from Tables 3A, 3B, 4A,4B, 5A, 5B, 6A, 6B, 7A, 7B, 8A, 8B, 10A, or 10B, or genes thatco-express with the at least one gene; wherein an expression level ofany gene in Tables 3A, 4A, 5A, 6A, 7A, 8A, and 10A is positivelyassociated with an increased risk of recurrence, and wherein anexpression level of any gene in Tables 3B, 4B, 5B, 6B, 7B 8B, and 10B isnegatively associated with a increased risk of recurrence.